Protein Information

Name smooth muscle actin
Synonyms ACTC; ACTC 1; ACTC1; Alpha cardiac actin; CMD1R; Smooth muscle actin; Alpha cardiac actins; Smooth muscle actins

Compound Information

Name carbon tetrachloride
CAS tetrachloromethane

Reference List

PubMed Abstract RScore(About this table)
18544128 Tutau F, Rodriguez-Ortigosa C, Puche JE, Juanarena N, Monreal I, Garcia Fernandez M, Clavijo E, Castilla A, Castilla-Cortazar I: Enhanced actions of insulin-like growth factor-I and interferon-alpha co-administration in experimental cirrhosis. Liver Int. 2009 Jan;29(1):37-46. Epub 2008 Jun 9.


METHODS: The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin, collagen, tissular inhibitor of metalloproteinases-1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection.
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19646978 Yasuda Y, Shimizu M, Sakai H, Iwasa J, Kubota M, Adachi S, Osawa Y, Tsurumi H, Hara Y, Moriwaki H: (-)-Epigallocatechin gallate prevents carbon tetrachloride-induced rat hepatic fibrosis by inhibiting the expression of the PDGFRbeta and IGF-1R. Chem Biol Interact. 2009 Dec 10;182(2-3):159-64. Epub 2009 Jul 30.

EGCG also decreased the expression of PDGFRbeta and alpha-smooth muscle actin proteins, thus indicating the inhibition of HSC activation.
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18397225 Tsai JH, Liu JY, Wu TT, Ho PC, Huang CY, Shyu JC, Hsieh YS, Tsai CC, Liu YC: Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats. J Viral Hepat. 2008 Jul;15(7):508-14. Epub 2008 Apr 4.

Moreover, silymarin significantly decreased the elevation of aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase in serum, and also reversed the altered expressions of alpha-smooth muscle actin in liver tissue.
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16579972 Kim KH, Kim HC, Hwang MY, Oh HK, Lee TS, Chang YC, Song HJ, Won NH, Park KK: The antifibrotic effect of TGF-beta1 siRNAs in murine model of liver cirrhosis. Biochem Biophys Res Commun. 2006 May 19;343(4):1072-8. Epub 2006 Mar 23.


In this experiment, the TGF-beta1 siRNAs reduced the expression of TGF-beta1 in the livers of CCl (4) injection compared with those of control group, and the expression of type I collagen and alpha-smooth muscle actin was decreased.
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19718641 Liu F, Liu ZD, Wu N, Cong X, Fei R, Chen HS, Wei L: Transplanted endothelial progenitor cells ameliorate carbon tetrachloride-induced liver cirrhosis in rats. Liver Transpl. 2009 Sep;15(9):1092-100.

EPCs reduced the expression of alpha-smooth muscle actin, collagen III, and transforming growth factor beta (P < 0.05) as well as levels of aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the serum (P < 0.05), but at the same time they increased the levels of albumin and Ki67.
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17973934 Zhang BJ, Xu D, Guo Y, Ping J, Chen LB, Wang H: Protection by and anti-oxidant mechanism of berberine against rat liver fibrosis induced by multiple hepatotoxic factors. Clin Exp Pharmacol Physiol. 2008 Mar;35(3):303-9. Epub 2007 Oct 30.


Liver biopsies were obtained for histological and immunohistochemical studies to detect the expressions of alpha-smooth muscle actin (SMA) and transforming growth factor (TGF)-beta1. 3.
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18812033 Yuan LP, Chen FH, Ling L, Bo H, Chen ZW, Li F, Zhong MM, Xia LJ: Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats. J Pharm Pharmacol. 2008 Oct;60(10):1393-402.

Moreover, TFB (80 and 160 mg kg (-1)) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-beta1 gene expression in the liver of liver fibrosis of rats.
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16256175 Noyan S, Cavusoglu I, Minbay FZ: The effect of vitamin A on CCl4-induced hepatic injuries in rats: a histochemical, immunohistochemical and ultrastructural study. Acta Histochem. 2006;107(6):421-34. Epub 2005 Oct 26.

Carbon tetrachloride intoxication was performed on rats for 2, 8, 12 or 20 weeks and 5x10 (4) IU vitamin A (as retinol palmitate) was injected subcutaneously once every 4 weeks.
Ito cells were detected by gold chloride impregnation, as well as desmin and alpha-smooth muscle actin (alpha-SMA) immunohistochemistry.
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17292878 Park EJ, Zhao YZ, Kim YC, Sohn DH: Bakuchiol-induced caspase-3-dependent apoptosis occurs through c-Jun NH2-terminal kinase-mediated mitochondrial translocation of Bax in rat liver myofibroblasts. Eur J Pharmacol. 2007 Mar 22;559(2-3):115-23. Epub 2007 Jan 23.


Bakuchiol, a prenylated phenolic terpene isolated from the seed of Psoralea corylifolia L. (Leguminosae), reduced activated hepatic stellate cells when treated to rats during liver injury recovery period as demonstrated by alpha-smooth muscle actin immunostaining in rat liver and induced apoptosis in activated hepatic stellate cells/myofibroblasts as demonstrated by DNA fragmentation, activation of caspase-3, release of cytochrome c into the cytoplasm, translocation of Bax into mitochondria, and the proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) in vitro.
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15112349 Liu QH, Li DG, Huang X, Zong CH, Xu QF, Lu HM: Suppressive effects of 17beta-estradiol on hepatic fibrosis in CCl4-induced rat model. World J Gastroenterol. 2004 May 1;10(9):1315-20.


Degrees of fibrosis and areas of hepatic stellate cells (HSCs) positive for alpha-smooth muscle actin (alpha-SMA) in the liver were determined by van Gieson (VG) stain and immunohistochemistry.
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19500642 Amin A, Mahmoud-Ghoneim D: Zizyphus spina-christi protects against carbon tetrachloride-induced liver fibrosis in rats. Food Chem Toxicol. 2009 Aug;47(8):2111-9. Epub 2009 Jun 13.

Furthermore, ZSC reduced the expression of alpha-smooth muscle actin, the deposition of types I and III collagen in CCl (4)-injured rats.
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19114984 Liu Y, Lui EL, Friedman SL, Li L, Ye T, Chen Y, Poon RT, Wo J, Kok TW, Fan ST: PTK787/ZK22258 attenuates stellate cell activation and hepatic fibrosis in vivo by inhibiting VEGF signaling. Lab Invest. 2009 Feb;89(2):209-21. Epub 2008 Dec 29.

In primary HSCs, PTK/ZK inhibited the expression of alpha-smooth muscle actin (alpha-SMA), collagen, tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as cell proliferation, migration and actin filament formation.
In a murine fibrotic liver, PTK/ZK attenuated collagen deposition and alpha-SMA expression in carbon tetrachloride-induced fibrosis in both a 'prevention' and 'treatment' dosing scheme.
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16609999 Zhang LJ, Zheng WD, Shi MN, Wang XZ: Effects of interleukin-10 on activation and apoptosis of hepatic stellate cells in fibrotic rat liver. World J Gastroenterol. 2006 Mar 28;12(12):1918-23.

AIM: To study the effects of interleukin-10 (IL-10) on the expression of alpha-smooth muscle actin (alpha-SMA), nuclear factor- kappa B (NF- kappa B) and Fas/Fas ligand (FasL) in hepatic stellate cells of experimental rats with hepatic fibrosis.
Fibrotic group was injected intraperitoneally with 50% carbon tetrachloride (CCl (4)) (2 mL/kg), twice a week.
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18097613 Doh KO, Jung HK, Moon IJ, Kang HG, Park JH, Park JG: Prevention of CCl4-induced liver cirrhosis by ribbon antisense to transforming growth factor-beta1. Int J Mol Med. 2008 Jan;21(1):33-9.


Immunohistochemical studies showed a reduced accumulation of collagen and alpha-smooth muscle actin.
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20058312 Gieling RG, Elsharkawy AM, Caamano JH, Cowie DE, Wright MC, Ebrahimkhani MR, Burt AD, Mann J, Raychaudhuri P, Liou HC, Oakley F, Mann DA: The c-Rel subunit of nuclear factor-kappaB regulates murine liver inflammation, wound-healing, and hepatocyte proliferation. Hepatology. 2010 Mar;51(3):922-31.

The subsequent fibrogenic/wound-healing response to both chronic carbon tetrachloride and bile duct ligation induced injury was also impaired and this was associated with deficiencies in the expression of fibrogenic genes, collagen I and alpha-smooth muscle actin, by hepatic stellate cells.
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19659781 Ginsburg I, Koren E, Horani A, Mahamid M, Doron S, Muhanna N, Amer J, Safadi R: Amelioration of hepatic fibrosis via Padma Hepaten is associated with altered natural killer T lymphocytes. Clin Exp Immunol. 2009 Jul;157(1):155-64.

Hepatic fibrosis was determined by sirius red staining of liver sections and by assessment of alpha smooth muscle actin expression compared with beta-actin (both by mRNA as well as the protein liver extract western blotting).
Hepatic fibrosis was induced by 6 weeks of biweekly i.p. carbon tetrachloride (CCl4) injections in male C57Bl6 mice.
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17223571 Xu D, Wu Y, Liao ZX, Wang H: Protective effect of verapamil on multiple hepatotoxic factors-induced liver fibrosis in rats. Pharmacol Res. 2007 Apr;55(4):280-6. Epub 2006 Dec 19.

Multiple hepatotoxic factors including carbon tetrachloride (CCl (4)), ethanol and high cholesterol were used to make the animal model of liver fibrosis.
Samples of the liver obtained by biopsy were subjected to histological and immunohistochemical studies for the expressions of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta (1) (TGF-beta (1)).
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18761555 Hu PF, Zhu YW, Zhong W, Chen YX, Lin Y, Zhang X, Yin C, Yue HY, Xie WF: Inhibition of plasminogen activator inhibitor-1 expression by siRNA in rat hepatic stellate cells. J Gastroenterol Hepatol. 2008 Dec;23(12):1917-25. Epub 2008 Aug 28.


Expression of alpha-smooth muscle actin, transforming growth factor-beta, tissue inhibitor of metalloproteinases-1, and collagen types I and III were evaluated by real-time PCR.
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16640026 Jiroutova A, Majdiakova L, Cermakova M, Kohlerova R, Kanta J: Expression of cytoskeletal proteins in hepatic stellate cells isolated from normal and cirrhotic rat liver. Acta Medica (Hradec Kralove). 2005;48(3-4):137-44.

We have studied the expression of alpha-smooth muscle actin and intermediate filament proteins vimentin, desmin and glial fibrillary acidic protein (GFAP) by immunocytochemistry in HSC cultured for 2 or 7 days after isolation.
Liver cirrhosis was produced in rats by repeated carbon tetrachloride administration.
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17112904 Zhan Y, Wang Y, Wei L, Chen H, Cong X, Fei R, Gao Y, Liu F: Differentiation of hematopoietic stem cells into hepatocytes in liver fibrosis in rats. Transplant Proc. 2006 Nov;38(9):3082-5.


The expressions of albumin (Alb), cytokeratin 8 (CK8), and alpha-smooth muscle actin (SMA) were determined by immunofluorescence methods.
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18503750 Yu J, Wu CW, Chu ES, Hui AY, Cheng AS, Go MY, Ching AK, Chui YL, Chan HL, Sung JJ: Elucidation of the role of COX-2 in liver fibrogenesis using transgenic mice. Biochem Biophys Res Commun. 2008 Aug 8;372(4):571-7. Epub 2008 May 27.

COX-2 transgenic (TG) mice that specifically overexpress the human COX-2 cDNA in the liver, knockout (KO), and wild type (WT) mice were studied in two different murine fibrosis models induced by carbon tetrachloride (CCl (4)) injection or methionine and choline-deficient (MCD) diet.
Hepatic stellate cell (HSC) activation was determined by immunohistochemical analysis of alpha-smooth muscle actin (alpha-SMA). mRNA expression of fibrogenic genes was assayed by real-time quantitative PCR.
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16941698 Zhang Y, Ikegami T, Honda A, Miyazaki T, Bouscarel B, Rojkind M, Hyodo I, Matsuzaki Y: Involvement of integrin-linked kinase in carbon tetrachloride-induced hepatic fibrosis in rats. Hepatology. 2006 Sep;44(3):612-22.

Immunohistochemical analysis of liver sections obtained from rats with CCl4-induced cirrhosis revealed increased expression and colocalization of ILK and alpha-smooth muscle actin in hepatic stellate cells in perisinusoidal areas.
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19164509 Nishikawa Y, Ohi N, Yagisawa A, Doi Y, Yamamoto Y, Yoshida M, Tokairin T, Yoshioka T, Omori Y, Enomoto K: Suppressive effect of orthovanadate on hepatic stellate cell activation and liver fibrosis in rats. Am J Pathol. 2009 Mar;174(3):881-90. Epub 2009 Jan 22.

When primary rat HSCs were cultured in the presence of 10% serum, they spontaneously lost characteristic stellate morphology, proliferated, and were transformed into an activated state with the formation of abundant stress fibers and increased expression of both alpha-smooth muscle actin and collagen type I mRNA.
We then examined whether OV could effectively suppress HSC activation in vivo after liver injury induced by either carbon tetrachloride or dimethylnitrosamine.
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18472332 Lam HB, Yeh CH, Cheng KC, Hsu CT, Cheng JT: Effect of cholinergic denervation on hepatic fibrosis induced by carbon tetrachloride in rats. Neurosci Lett. 2008 Jun 13;438(1):90-5. Epub 2008 Apr 18.

The immunohistochemical staining for alpha smooth muscle actin (alphaSMA) indicated the less HSCs in CCl (4) treated rat liver with cholinergic denervation as compared to the sham-operated CCl (4) treated rats.
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19736546 Goo MJ, Ki MR, Lee HR, Yang HJ, Yuan DW, Hong IH, Park JK, Hong KS, Han JY, Hwang OK, Kim DH, Do SH, Cohn RD, Jeong KS: Helicobacter pylori promotes hepatic fibrosis in the animal model. Lab Invest. 2009 Nov;89(11):1291-303. Epub 2009 Sep 7.

To elucidate the pathological effect of H. pylori infection on the progression of hepatic fibrosis, C57BL/6 mice and Sprague-Dawley rats were orally inoculated with H. pylori, and hepatic fibrosis was induced with carbon tetrachloride (CCl (4)) administration.
Compared with the CCl (4)-treated group, alpha-smooth muscle actin and transforming growth factor-beta1 were enhanced; however, senescence marker protein-30, a multifunctional protein protecting hepatocytes against oxidative stress and apoptosis, was suppressed in the CCl (4)+H. pylori group.
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17174718 Lv P, Luo HS, Zhou XP, Xiao YJ, Paul SC, Si XM, Zhou YH: Reversal effect of thalidomide on established hepatic cirrhosis in rats via inhibition of nuclear factor-kappaB/inhibitor of nuclear factor-kappaB pathway. Arch Med Res. 2007 Jan;38(1):15-27.

METHODS: Rat liver cirrhosis was achieved by IP injection of carbon tetrachloride (CCl4) three times weekly for 8 weeks.
NF-kappaBp65, ICAM-1, VCAM-1 and alpha-smooth muscle actin (alpha-SMA) protein in the liver, IkappaBalpha protein in cytoplasm and NF-kappaBp65 protein in nucleus and ICAM-1, VCAM-1 mRNA levels in the liver were studied using immunohistochemistry, Western blot, and reverse transcriptase polymerase chain reaction, respectively.
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16124045 Shen XH, Cheng WF, Li XH, Sun JQ, Li F, Ma L, Xie LM: Effects of dietary supplementation with vitamin E and selenium on rat hepatic stellate cell apoptosis. World J Gastroenterol. 2005 Aug 28;11(32):4957-61.

METHODS: An acute liver damage model of rats was established by intraperitoneal injection of carbon tetrachloride (0.3 mL/100 g body weight) twice a week, then the rats were killed at 6, 24, 48, and 72 h after the first and third injection, respectively.
Activated HSCs were determined by alpha-smooth muscle actin immunohistochemistry staining.
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19413596 Zhao XY, Zeng X, Li XM, Wang TL, Wang BE: Pirfenidone inhibits carbon tetrachloride- and albumin complex-induced liver fibrosis in rodents by preventing activation of hepatic stellate cells. Clin Exp Pharmacol Physiol. 2009 Oct;36(10):963-8. Epub 2009 Apr 27.

Pirfenidone significantly inhibited the expression of a-smooth muscle actin and Type I collagen in 8 ng/mL transforming growth factor-beta1- or 5% fetal bovine serum-activated LX-2 cells in a dose-dependent manner. 5.
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19416217 Bennett RG, Heimann DG, Tuma DJ: Relaxin reduces fibrosis in models of progressive and established hepatic fibrosis. Ann N Y Acad Sci. 2009 Apr;1160:348-9.


In the prevention study, relaxin reduced collagen and smooth muscle actin content and significantly reduced serum levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase.
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19359429 Watanabe A, Sohail MA, Gomes DA, Hashmi A, Nagata J, Sutterwala FS, Mahmood S, Jhandier MN, Shi Y, Flavell RA, Mehal WZ: Inflammasome-mediated regulation of hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1248-57. Epub 2009 Apr 9.

Twenty-four hours later primary mouse HSC were stained with alpha-smooth muscle actin and visualized by confocal microscopy, and TGF-beta and collagen1 mRNA expression was quantified.
Finally, we confirmed an important role of the inflammasome in experimental liver fibrosis by the injection of carbon tetrachloride (CCl (4)) or thioacetamide (TAA) in wild-type mice and mice lacking components of the inflammasome.
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16676162 Young SC, Wang CJ, Lin JJ, Peng PL, Hsu JL, Chou FP: Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats. Arch Toxicol. 2007 Jan;81(1):45-55. Epub 2006 May 5.

The histological examination showed the PBL extract protected liver from the damage induced by CCl (4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver.
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19134051 Vanheule E, Geerts AM, Van Huysse J, Schelfhout D, Praet M, Van Vlierberghe H, De Vos M, Colle I: An intravital microscopic study of the hepatic microcirculation in cirrhotic mice models: relationship between fibrosis and angiogenesis. Int J Exp Pathol. 2008 Dec;89(6):419-32.

Cirrhosis was induced by subcutaneous injection of carbon tetrachloride (CCl (4)) and by common bile duct ligation (CBDL) in mice.
Thereafter, liver samples were taken for sirius red, CD31, Ki67, vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (alpha-SMA) evaluation by immunohistochemistry (IHC).
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17058265 Choi SS, Sicklick JK, Ma Q, Yang L, Huang J, Qi Y, Chen W, Li YX, Goldschmidt-Clermont PJ, Diehl AM: Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice. Hepatology. 2006 Nov;44(5):1267-77.

To achieve this, we used transgenic mice that express constitutively active human Rac1 under the control of the alpha-smooth muscle actin (alpha-sma) promoter, because alpha-sma expression is induced spontaneously during HSC activation.
Similarly, Rac mice treated with carbon tetrachloride (CCl (4)) accumulated greater numbers of activated HSCs and had more liver damage, hepatocyte apoptosis, and liver fibrosis-as well as higher mortality-than CCl (4)-treated wild-type mice.
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17922224 Wu LM, Wu XX, Sun Y, Kong XW, Zhang YH, Xu Q: A novel synthetic oleanolic acid derivative (CPU-II2) attenuates liver fibrosis in mice through regulating the function of hepatic stellate cells. J Biomed Sci. 2008 Mar;15(2):251-9. Epub 2007 Oct 6.


CPU-II2 also attenuated the mRNA expression of alpha-smooth muscle actin (alpha-SMA) and tissue inhibitor of metalloproteinase type 1 (TIMP-1) induced by CCl4 in mice and reduced both mRNA and protein levels of alpha-SMA in HSC-T6 cells.
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15312518 Zhang RP, Zhang WH, Xue DB, Wei YW: [Morphology of portal hypertension at the early stage of liver damage induced by CCl4: an experimental study with dogs]. Zhonghua Yi Xue Za Zhi. 2004 Jul 2;84(13):1118-21.

METHODS: Sixteen mongrel dogs were injected intraperitoneally with carbon tetrachloride (CCl (4)) once a week for 4 weeks and then once every 4 days, totally for 7 weeks.
Before the experiment and 7 weeks after the beginning of experiment, small pieces of liver tissues were taken through a median upper abdominal incision and underwent HE staining, Masson's staining, and immunohistochemistry with alpha-smooth muscle actin (alpha-SMA) to label the activated astrocyte (hepatic stellate cell, HSC), and transmission electron microscopy.
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15479692 Duplantier JG, Dubuisson L, Senant N, Freyburger G, Laurendeau I, Herbert JM, Desmouliere A, Rosenbaum J: A role for thrombin in liver fibrosis. . Gut. 2004 Nov;53(11):1682-7.


Fibrosis and the area occupied by alpha smooth muscle actin (ASMA) positive cells were quantified with histomorphometry.
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20178458 Rabani V, Shahsavani M, Gharavi M, Piryaei A, Azhdari Z, Baharvand H: Mesenchymal stem cell infusion therapy in carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression. Cell Biol Int. 2010 Feb 23.

The expression of alphaSMA (smooth muscle actin) and TIMP1 was also downregulated in the CCl4/MSC group.
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19815628 Choi SS, Omenetti A, Witek RP, Moylan CA, Syn WK, Jung Y, Yang L, Sudan DL, Sicklick JK, Michelotti GA, Rojkind M, Diehl AM: Hedgehog pathway activation and epithelial-to-mesenchymal transitions during myofibroblastic transformation of rat hepatic cells in culture and cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2009 Dec;297(6):G1093-106. Epub 2009 Oct 8.


Q-HSC activation in vitro (culture) and in vivo (CCl (4)-induced cirrhosis) resulted in decreased expression of Hh-interacting protein (Hhip, an Hh antagonist), the EMT inhibitors bone morphogenic protein (BMP-7) and inhibitor of differentiation (Id2), the adherens junction component E-cadherin, and epithelial keratins 7 and 19 and increased expression of Gli2 (an Hh target gene) and mesenchymal markers, including the mesenchyme-associated transcription factors Lhx2 and Msx2, the myofibroblast marker alpha-smooth muscle actin, and matrix molecules such as collagen.
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15983038 Nieto N, Cederbaum AI: S-adenosylmethionine blocks collagen I production by preventing transforming growth factor-beta induction of the COL1A2 promoter. J Biol Chem. 2005 Sep 2;280(35):30963-74. Epub 2005 Jun 27.

To study the anti-fibrogenic mechanisms of S-adenosylmethionine (AdoMet), transgenic mice harboring the -17 kb to +54 bp of the collagen alpha2 (I) promoter (COL1A2) cloned upstream from the beta-gal reporter gene were injected with carbon tetrachloride (CCl4) to induce fibrosis and coadministered either AdoMet or saline.
Incubation of primary stellate cells with AdoMet down-regulated basal and TGFbeta-induced collagen I and alpha-smooth muscle actin proteins.
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19462446 Hong JJ, Pan FY, Qian Y, Cheng LC, Zhang HX, Xue B, Li CJ: Overexpression of beta-catenin is responsible for the development of portal hypertension during liver cirrhosis. Anat Rec. 2009 Jun;292(6):818-26.


In this study, we examined the expression of beta-catenin in human cirrhotic livers, and administered adenoviruses carrying the beta-catenin or DeltaTCF4 genes to cirrhotic rats to investigate the role of beta-catenin in the development of liver cirrhosis development. beta-catenin expression was associated with liver cirrhosis development in cirrhotic human and rat liver. beta-catenin adenovirus was capable of accelerating cirrhosis progress but this progression was unaffected by administration of DeltaTCF4 adenovirus. beta-catenin was mainly located in the intercellular regions between liver cells and was highly concentrated in the hepatic sinusoid wall, where alpha-smooth muscle actin (SMA) was also mainly distributed.
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16381635 Liu SQ, Yu JP, He L, Yu HG, Luo HS: [Effects of nuclear factor kappaB and transforming growth factor beta1 in the anti-liver fibrosis process using Ginkgo biloba extract]. Zhonghua Gan Zang Bing Za Zhi. 2005 Dec;13(12):903-7.


The expressions of nuclear factor kappaB (NF-kappaB) P65, and alpha-smooth muscle actin (alpha-SMA) were detected by immunohistochemistry.
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19747501 Domitrovic R, Jakovac H, Tomac J, Sain I: Liver fibrosis in mice induced by carbon tetrachloride and its reversion by luteolin. Toxicol Appl Pharmacol. 2009 Dec 15;241(3):311-21. Epub 2009 Sep 8.

Concomitantly, the expression of glial fibrillary acidic protein and alpha-smooth muscle actin indicated deactivation of hepatic stellate cells.
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19567170 Deng ZY, Li J, Jin Y, Chen XL, Lu XW: Effect of oxymatrine on the p38 mitogen-activated protein kinases signalling pathway in rats with CCl4 induced hepatic fibrosis. Chin Med J. 2009 Jun 20;122(12):1449-54.


We obesrved changes in deposition of collagen, hyaluronic acid (HA), laminin (LN), collagen type IV (CIV), procollagen III (PCIII) and hydroxyproline (Hyp), a-smooth muscle actin (alpha-SMA) and phosphor-p38 (pp38).
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17565644 Tu CT, Guo JS, Wang M, Wang JY: Antifibrotic activity of rofecoxib in vivo is associated with reduced portal hypertension in rats with carbon tetrachloride-induced liver injury. J Gastroenterol Hepatol. 2007 Jun;22(6):877-84.

The activated, alpha smooth muscle actin (alpha-SMA) positive hepatic stellate cells (HSCs) and the protein levels of collagen types I, III, IV, as well as laminin and two fibrogenic mediators, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) in the livers, were detected with immunohistochemical staining and western blot methods, respectively.
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19808650 Mitchell C, Robin MA, Mayeuf A, Mahrouf-Yorgov M, Mansouri A, Hamard M, Couton D, Fromenty B, Gilgenkrantz H: Protection against hepatocyte mitochondrial dysfunction delays fibrosis progression in mice. Am J Pathol. 2009 Nov;175(5):1929-37. Epub 2009 Oct 1.

We induced liver fibrogenesis by chronic carbon tetrachloride treatment (3 or 6 weeks of biweekly injections) in transgenic mice expressing Bcl-2 in their hepatocytes or in normal control mice.
Picrosirius red staining, alpha-smooth muscle actin immunohistochemistry, and real-time PCR for transforming growth factor-beta and collagen alpha-I revealed that Bcl-2 transgenic mice presented reduced fibrosis at early stages of fibrogenesis.
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15860571 Fiorucci S, Rizzo G, Antonelli E, Renga B, Mencarelli A, Riccardi L, Orlandi S, Pruzanski M, Morelli A, Pellicciari R: A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis. J Pharmacol Exp Ther. 2005 Aug;314(2):584-95. Epub 2005 Apr 28.


Exposure of HSCs to FXR ligands increases small heterodimer partner (SHP) mRNA by 3-fold and reduces basal and thrombin-stimulated expression of alpha1 (I) collagen, alpha-smooth muscle actin (alpha-SMA), TIMP-1, and TIMP-2 by approximately 60 to 70%, whereas it increased matrix metalloprotease (MMP)-2 activity by 2-fold.
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16609998 Cheung PY, Zhang Q, Zhang YO, Bai GR, Lin MC, Chan B, Fong CC, Shi L, Shi YF, Chun J, Kung HF, Yang M: Effect of WeiJia on carbon tetrachloride induced chronic liver injury. World J Gastroenterol. 2006 Mar 28;12(12):1912-7.

Alpha smooth muscle actin (alpha-SMA) and proliferating cell nuclear antigen (PCNA) immunohistochemistry were also performed.
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18804890 Iwaisako K, Hatano E, Taura K, Nakajima A, Tada M, Seo S, Tamaki N, Sato F, Ikai I, Uemoto S, Kinoshita M: Loss of Sept4 exacerbates liver fibrosis through the dysregulation of hepatic stellate cells. J Hepatol. 2008 Nov;49(5):768-78. Epub 2008 Jul 15.

METHODS: We analyzed the expression of alpha-smooth muscle actin (alpha-SMA), collagens and other markers in primary cultured HSCs derived from wild-type and Sept4 (-/-) mice.
We compared susceptibility of these mice to liver fibrosis induced by either carbon tetrachloride treatment, bile duct ligation or methionine/choline-deficient diet.
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16508911 Lee TH, Jawan B, Chou WY, Lu CN, Wu CL, Kuo HM, Concejero AM, Wang CH: Alpha-melanocyte-stimulating hormone gene therapy reverses carbon tetrachloride induced liver fibrosis in mice. J Gene Med. 2006 Jun;8(6):764-72.

Following gene transfer, both the activation of alpha-smooth muscle actin (alpha-SMA) and cyclooxygenase-2 (COX-2) was significantly attenuated.
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15952662 Shen XH, Cheng WF, Li XH, Xie LM, Sun J, Li F, Ma L: [Effect of antioxidant on hepatic stellate cell proliferation and apoptosis during recovery from liver fibrosis]. Wei Sheng Yan Jiu. 2005 Mar;34(2):194-6.


METHODS: Activated HSC was determined by alpha-smooth muscle actin immunohistochemistry staining and apoptotic HSC determined by dual staining both of the terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL) and of alpha-smooth muscle actin immunohistochemistry.
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17944888 Hsiao Y, Zou T, Ling CC, Hu H, Tao XM, Song HY: Disruption of tissue-type plasminogen activator gene in mice aggravated liver fibrosis. J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 2):e258-64. Epub 2007 Oct 17.

The aim of this study is to investigate the role of tPA in carbon tetrachloride (CCl (4))-induced liver fibrosis.
Deficiency of tPA increased alpha-smooth muscle actin expression in the mice livers.
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15646798 Lee KJ, Kim JY, Jung KS, Choi CY, Chung YC, Kim DH, Jeong HG: Suppressive effects of Platycodon grandiflorum on the progress of carbon tetrachloride-induced hepatic fibrosis. Arch Pharm Res. 2004 Dec;27(12):1238-44.

CK also significantly prevented the elevation of hepatic alpha1 (I) procollagen (type I collagen) mRNA and alpha-smooth muscle actin (alpha-SMA) expressions in the liver of CCl4-intoxicated rats and also suppressed the induction of alpha-SMA and type I collagen in cultured hepatic stellate cells, in dose-dependent manners.
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17334410 Hattori S, Dhar DK, Hara N, Tonomoto Y, Onoda T, Ono T, Yamanoi A, Tachibana M, Tsuchiya M, Nagasue N: FR-167653, a selective p38 MAPK inhibitor, exerts salutary effect on liver cirrhosis through downregulation of Runx2. Lab Invest. 2007 Jun;87(6):591-601. Epub 2007 Mar 5.

In this study, we evaluated the salutary effect of FR-167653 (FR), a selective p38 inhibitor, in a carbon tetrachloride (CCl (4))-induced rat cirrhotic model.
Significant dose-dependent reduction in alpha-smooth muscle actin immunostaining and hydroxyproline content of the liver was noticed in the FR-treated rats.
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17869086 Yun HS, Do SH, Jeong WI, Yang HJ, Yuan DW, Hong IH, Lee HR, Lee IS, Kim YK, Choi MS, Kim HA, Jeong KS: Cytotoxic effects of the conjugated linoleic acid isomers t10c12, c9t11-CLA and mixed form on rat hepatic stellate cells and CCl4-induced hepatic fibrosis. J Nutr Biochem. 2008 Mar;19(3):175-83. Epub 2007 Sep 14.

In the CLA-supplemented rat livers, alpha-smooth muscle actin-positive cells were significantly reduced around the portal vein.
In order to evaluate the protective effect of CLA on carbon tetrachloride (CCl4)-induced hepatic fibrosis in vivo, animals were treated with 10% CCl4 to induce hepatic fibrosis during all experimental periods.
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18703754 Hauso O, Gustafsson BI, Nordrum IS, Waldum HL: The effect of terguride in carbon tetrachloride-induced liver fibrosis in rat. Exp Biol Med. 2008 Nov;233(11):1385-8. Epub 2008 Aug 14.

The extent of fibrosis was evaluated by liver weight, histologic analysis, biochemical analysis, and alpha-smooth muscle actin (alpha-SMA) immunohistochemistry.
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17060319 Zhou X, Jamil A, Nash A, Chan J, Trim N, Iredale JP, Benyon RC: Impaired proteolysis of collagen I inhibits proliferation of hepatic stellate cells: implications for regulation of liver fibrosis. J Biol Chem. 2006 Dec 29;281(52):39757-65. Epub 2006 Oct 23.


Of the stellate cell activation markers examined (tissue inhibitor of metalloproteinases-1, alpha-smooth muscle actin, matrix metalloproteinases-2 and -9, and procollagen I) only the last was decreased by culture on r/r collagen relative to normal collagen I.
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17976157 Hagiwara S, Otsuka T, Yamazaki Y, Kosone T, Sohara N, Ichikawa T, Sato K, Kakizaki S, Takagi H, Mori M: Overexpression of NK2 promotes liver fibrosis in carbon tetrachloride-induced chronic liver injury. Liver Int. 2008 Jan;28(1):126-31. Epub 2007 Nov 1.

The protein levels of alpha-smooth muscle actin (alpha-SMA), c-Met and its phosphorylation were determined by Western blot analysis.
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16539848 Chou WY, Lu CN, Lee TH, Wu CL, Hung KS, Concejero AM, Jawan B, Wang CH: Electroporative interleukin-10 gene transfer ameliorates carbon tetrachloride-induced murine liver fibrosis by MMP and TIMP modulation. Acta Pharmacol Sin. 2006 Apr;27(4):469-76.

Following gene transfer, both the activation of alpha-smooth muscle actin and cyclooxygenase-2 were significantly attenuated.
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17038628 Horani A, Muhanna N, Pappo O, Melhem A, Alvarez CE, Doron S, Wehbi W, Dimitrios K, Friedman SL, Safadi R: Beneficial effect of glatiramer acetate (Copaxone) on immune modulation of experimental hepatic fibrosis. Am J Physiol Gastrointest Liver Physiol. 2007 Feb;292(2):G628-38. Epub 2006 Oct 12.

Hepatic fibrosis was induced in C57BL/6 mice by intraperitoneal administration of carbon tetrachloride (CCl (4)) for 6 wk.
By morphometric measurement of Sirius red-stained tissue sections, the relative fibrosis area decreased from 5.28 +/- 0.32% (mean +/- SE) in the untreated CCl (4) group to 2.01 +/- 0.28% in CCl (4)+GA-treated animals, compared with 0.38 +/- 0.07% in naive mice. alpha-Smooth muscle actin immunoblotting and mRNA expression revealed a similar pattern.
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18266971 Hamzavi J, Ehnert S, Godoy P, Ciuclan L, Weng H, Mertens PR, Heuchel R, Dooley S: Disruption of the Smad7 gene enhances CCI4-dependent liver damage and fibrogenesis in mice. J Cell Mol Med. 2008 Oct;12(5B):2130-44. Epub 2008 Feb 4.

CCI4-dependent Smad2 phosphorylation was pronounced in S7DeltaE1 mice and accompanied by increased numbers of alpha-smooth muscle actin positive 'activated' HSCs.
To obtain insight into Smad7-depend-ent protective effects, chronic liver damage was induced in mice by carbon tetrachloride (CCI4) administration.
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17631135 Nakamura T, Torimura T, Sakamoto M, Hashimoto O, Taniguchi E, Inoue K, Sakata R, Kumashiro R, Murohara T, Ueno T, Sata M: Significance and therapeutic potential of endothelial progenitor cell transplantation in a cirrhotic liver rat model. Gastroenterology. 2007 Jul;133(1):91-107.e1. Epub 2007 Apr 11.

METHODS: Recipient rats were injected intraperitoneally with carbon tetrachloride (CCl (4)) twice weekly for 6 weeks before initial administration of EPCs.
Single and multiple EPC transplantation rats had reduced liver fibrosis, with decreased alpha2-(I)-procollagen, fibronectin, transforming growth factor-beta, and alpha-smooth muscle actin-positive cells.
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19587308 Salameh N, Larrat B, Abarca-Quinones J, Pallu S, Dorvillius M, Leclercq I, Fink M, Sinkus R, Van Beers BE: Early detection of steatohepatitis in fatty rat liver by using MR elastography. Radiology. 2009 Oct;253(1):90-7. Epub 2009 Jul 8.

Fifty-four rats were imaged after being fed either a standard diet, a choline-deficient diet for up to 8 weeks to induce steatohepatitis, or a 2-week orotic acid diet to induce steatosis; or were imaged 48 hours after carbon tetrachloride injection to model acute liver injury.
Myofibroblast activation was assessed with morphometric analysis of alpha-smooth muscle actin.
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19399744 Tsai PC, Fu TW, Chen YM, Ko TL, Chen TH, Shih YH, Hung SC, Fu YS: The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis. Liver Transpl. 2009 May;15(5):484-95.

We investigated the effect of human umbilical mesenchymal stem cells (HUMSCs) from Wharton's jelly on carbon tetrachloride (CCl4)-induced liver fibrosis in rats.
Moreover, rats in the CCl4 (8W)+HUMSC (liver) group had significantly lower levels of serum glutamic oxaloacetic transaminase, glutamic pyruvate transaminase, alpha-smooth muscle actin, and transforming growth factor-beta1 in the liver, whereas the expression of hepatic mesenchymal epithelial transition factor-phosphorylated type (Met-P) and hepatocyte growth factor was up-regulated, in comparison with the CCl4 (8W) group.
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17437422 Muhanna N, Horani A, Doron S, Safadi R: Lymphocyte-hepatic stellate cell proximity suggests a direct interaction. . Clin Exp Immunol. 2007 May;148(2):338-47.

To investigate lymphocyte/hepatic stellate cell (HSC) interactions, hepatic fibrosis was induced by administering carbon tetrachloride (CCl4) intraperitoneally (i.p.) for 4 weeks in C57Bl/6 mice.
Confocal microscopy was used to evaluate alpha smooth-muscle actin (alphaSMA) and lymphocyte subsets in liver sections.
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18929613 Shyu MH, Kao TC, Yen GC: Hsian-tsao (Mesona procumbens Heml.) prevents against rat liver fibrosis induced by CCl (4) via inhibition of hepatic stellate cells activation. Food Chem Toxicol. 2008 Dec;46(12):3707-13. Epub 2008 Sep 26.

In this study, the protective effect of extract of Hsian-tsao (Mesona procumbens) (EHT) against liver fibrogenesis in carbon tetrachloride (CCl (4))-injured rats was evaluated.
Oral administration of EHT reduced the levels of alpha-smooth muscle actin (alpha-SMA) and the activity of metalloproteinases (MMPs) in rats injured by treatment with CCl (4).
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18622026 Shan W, Palkar PS, Murray IA, McDevitt EI, Kennett MJ, Kang BH, Isom HC, Perdew GH, Gonzalez FJ, Peters JM: Ligand activation of peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) attenuates carbon tetrachloride hepatotoxicity by downregulating proinflammatory gene expression. Toxicol Sci. 2008 Oct;105(2):418-28. Epub 2008 Jul 12.

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18042797 Miyata E, Masuya M, Yoshida S, Nakamura S, Kato K, Sugimoto Y, Shibasaki T, Yamamura K, Ohishi K, Nishii K, Ishikawa F, Shiku H, Katayama N: Hematopoietic origin of hepatic stellate cells in the adult liver. . Blood. 2008 Feb 15;111(4):2427-35. Epub 2007 Nov 27.


To test this hypothesis, we generated chimeric mice by transplantation of clonal populations of cells derived from single enhanced green fluorescent protein (EGFP)-marked Lin (-) Sca-1 (+) c-kit (+) CD34 (-) cells and examined the histology of liver tissues obtained from the chimeric mice with carbon tetrachloride (CCl (4))-induced injury.
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16484506 Leclercq IA, Sempoux C, Starkel P, Horsmans Y: Limited therapeutic efficacy of pioglitazone on progression of hepatic fibrosis in rats. Gut. 2006 Jul;55(7):1020-9. Epub 2006 Feb 16.


METHODS: Repeated injections of carbon tetrachloride (CCl4), a choline deficient diet, or bile duct ligation (BDL) were used to induce hepatic fibrosis in rats.
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19786014 Shi H, Dong L, Bai Y, Zhao J, Zhang Y, Zhang L: Chlorogenic acid against carbon tetrachloride-induced liver fibrosis in rats. Eur J Pharmacol. 2009 Nov 25;623(1-3):119-24. Epub 2009 Sep 26.

Intragastric administration of CGA reduced the protein expression of alpha-smooth muscle actin (alpha-SMA) and glucose-regulated proteins 78 and 94 (GRP78 and GRP94) in rats injured by treatment with CCl (4).
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19116891 Moles A, Tarrats N, Fernandez-Checa JC, Mari M: Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential. Hepatology. 2009 Apr;49(4):1297-307.


Here, we show that expression of cathepsin B (CtsB) and cathepsin D (CtsD) is negligible in quiescent HSCs but parallels the increase of alpha-smooth muscle actin and transforming growth factor-beta during in vitro mouse HSC activation.
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19141029 Yan Y, Xu W, Qian H, Si Y, Zhu W, Cao H, Zhou H, Mao F: Mesenchymal stem cells from human umbilical cords ameliorate mouse hepatic injury in vivo. Liver Int. 2009 Mar;29(3):356-65. Epub 2008 Dec 29.

METHODS: Human umbilical cord-derived mesenchymal stem cells, characterized by flow cytometry, were transplanted into carbon tetrachloride (CCl (4))-injured mice, and then followed for determination of localization and differentiation.
Under conditions favouring differentiation in vivo, the expression of tryptophan 2,3-dioxygenase, human alpha-fetoprotein, cytokeratin 18, fibroblast secretory protein 1 and alpha-smooth-muscle-actin was detectable after hUCMSCs administration to mice subjected to liver injury.
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18427963 Bahcecioglu IH, Koca SS, Poyrazoglu OK, Yalniz M, Ozercan IH, Ustundag B, Sahin K, Dagli AF, Isik A: Hepatoprotective effect of infliximab, an anti-TNF-alpha agent, on carbon tetrachloride-induced hepatic fibrosis. Inflammation. 2008 Aug;31(4):215-21. Epub 2008 Apr 22.

The scores of hepatic necrosis, inflammation and fibrosis, and expression of alpha-smooth muscle actin were lower in the infliximab-treated group than the CCI (4)-treated group (p <0.01, p <0.001, p <0.01, p <0.001, respectively).
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16943688 Paul SC, Lv P, Xiao YJ, An P, Liu SQ, Luo HS: Thalidomide in rat liver cirrhosis: blockade of tumor necrosis factor-alpha via inhibition of degradation of an inhibitor of nuclear factor-kappaB. Pathobiology. 2006;73(2):82-92.

METHODS: Liver cirrhosis was achieved by intraperitoneal injection of carbon tetrachloride thrice weekly, and thalidomide (10 or 100 mg/kg/day) was given daily by intragastric route for 8 weeks.
Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), prealbumin (PA), hyaluronic acid (HA) and laminin (LN), and hydroxyproline (HYP), NF-kappaBp65, alpha-smooth muscle actin (alpha-SMA) protein and TNF-alpha mRNA were studied in the liver, IkappaBalpha and TNF-alpha protein in the cytoplasm and NF-kappaBp65 protein in the nucleus.
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18481824 Sun C, Li DG, Chen YW, Chen YW, Wang BC, Sun QL, Lu HM: Transplantation of urokinase-type plasminogen activator gene-modified bone marrow-derived liver stem cells reduces liver fibrosis in rats. J Gene Med. 2008 Aug;10(8):855-66.

The expression of alpha-smooth muscle actin protein, transforming growth factor-beta1 protein and collagen types I and III mRNA were downregulated.
In the present study, we investigated the therapeutic effects of uPA gene-modified BDLSC transplantation on carbon tetrachloride (CCl4)-induced liver fibrosis in rats.
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19670427 Tong Z, Chen R, Alt DS, Kemper S, Perbal B, Brigstock DR: Susceptibility to liver fibrosis in mice expressing a connective tissue growth factor transgene in hepatocytes. Hepatology. 2009 Sep;50(3):939-47.


However, after chronic administration of CCl (4), alpha-smooth muscle actin (alpha-SMA)-expressing cells and collagen deposition were increased as a function of the dosage of the hCCN2 transgene (hccn2 (+/+) > hccn2 (+/-) > hccn2 (-/-)).
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18485088 Anstee QM, Goldin RD, Wright M, Martinelli A, Cox R, Thursz MR: Coagulation status modulates murine hepatic fibrogenesis: implications for the development of novel therapies. J Thromb Haemost. 2008 Aug;6(8):1336-43. Epub 2008 May 14.

Prothrombotic FV Leiden mutant mice, C57BL/6 control animals and anticoagulated mice were studied after chronic exposure to carbon tetrachloride.
Changes in the fibrosis scores were mirrored by changes in liver hydroxyproline content and hepatic stellate cell activation detected by alpha-smooth muscle actin expression.
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15591519 Sanz S, Pucilowska JB, Liu S, Rodriguez-Ortigosa CM, Lund PK, Brenner DA, Fuller CR, Simmons JG, Pardo A, Martinez-Chantar ML, Fagin JA, Prieto J: Expression of insulin-like growth factor I by activated hepatic stellate cells reduces fibrogenesis and enhances regeneration after liver injury. Gut. 2005 Jan;54(1):134-41.


BACKGROUND/AIM: Hepatic stellate cells (HSCs) express alpha-smooth muscle actin (alphaSMA) and acquire a profibrogenic phenotype upon activation by noxious stimuli.
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19192169 Li YL, Wu J, Wei D, Zhang DW, Feng H, Chen ZN, Bian H: Newcastle disease virus represses the activation of human hepatic stellate cells and reverses the development of hepatic fibrosis in mice. Liver Int. 2009 Apr;29(4):593-602. Epub 2009 Jan 28.

Activated HSCs facilitated the replication of NDV, thereby repressing the secretion of MMP, the expression of these indices for hepatic fibrosis and the expression of alpha-SMA and collagen fibrils in hepatic fibrosis of the mouse induced by carbon tetrachloride.
Colocalization of NDV virions and alpha-smooth muscle actin (alpha-SMA) were detected by double immunofluorescence staining.
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20144743 Pulavendran S, Vignesh J, Rose C: Differential anti-inflammatory and anti-fibrotic activity of transplanted mesenchymal vs. hematopoietic stem cells in carbon tetrachloride-induced liver injury in mice. Int Immunopharmacol. 2010 Apr;10(4):513-9. Epub 2010 Feb 6.

Immunostaining for the expression of tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), alpha smooth muscle actin (alpha-SMA) and type I collagen proteins was carried out and the expression of these mRNAs was also studied.
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15633229 Shi GF, Li Q: Effects of oxymatrine on experimental hepatic fibrosis and its mechanism in vivo. World J Gastroenterol. 2005 Jan 14;11(2):268-71.

METHODS: Thirty-two rats were randomly divided into four groups; 16 were used to develop hepatic fibrosis by carbon tetrachloride (CCl4) and treated with or without OM, and 16 were used as controls.
The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and alpha-smooth muscle actin (alpha-SMA) in the livers of rats was detected by immunohistochemical assay.
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16420518 Hui AY, Leung WK, Chan HL, Chan FK, Go MY, Chan KK, Tang BD, Chu ES, Sung JJ: Effect of celecoxib on experimental liver fibrosis in rat. Liver Int. 2006 Feb;26(1):125-36.

Expression of COX-2, alpha smooth muscle actin and connective tissue growth factor (CTGF) was evaluated by immunohistochemistry.
RESULTS: Liver fibrosis was significantly worse in rats that received both carbon tetrachloride (CCl4) and celecoxib, compared with rats that received CCl4 and gavage of water (P = 0.037).
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17698563 Safadi R, Zigmond E, Pappo O, Shalev Z, Ilan Y: Amelioration of hepatic fibrosis via beta-glucosylceramide-mediated immune modulation is associated with altered CD8 and NKT lymphocyte distribution. Int Immunol. 2007 Aug;19(8):1021-9. Epub 2007 Aug 13.

Western blot analysis for alpha smooth muscle actin from liver extracts followed a similar pattern, increasing in groups A-E.
METHODS: Hepatic fibrosis was induced by biweekly intra-peritoneal (IP) carbon tetrachloride (CCl (4)) administrations for 7 weeks in 5 groups (A-E) of male C57Bl/6 mice.
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19506795 Tanaka N, Kono H, Ishii K, Hosomura N, Fujii H: Dietary olive oil prevents carbon tetrachloride-induced hepatic fibrosis in mice. J Gastroenterol. 2009;44(9):983-90. Epub 2009 Jun 9.

The expression of alpha-smooth muscle actin (alpha-SMA) was assessed by immunohistochemistry.
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15832415 Yao XX, Lv T: Effects of pharmacological serum from normal and liver fibrotic rats on HSCs. World J Gastroenterol. 2005 Apr 28;11(16):2444-9.

METHODS: Some rats were induced with liver fibrosis: 40% carbon tetrachloride (CCl4) subcutaneous injection, twice a week for 9 wk.
The rates of proliferation and expression of alpha-smooth muscle actin (alpha-SMA) were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and immunocytochemistry stain, respectively.
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19650157 Osterreicher CH, Taura K, De Minicis S, Seki E, Penz-Osterreicher M, Kodama Y, Kluwe J, Schuster M, Oudit GY, Penninger JM, Brenner DA: Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice. Hepatology. 2009 Sep;50(3):929-38.

Liver pathology was analyzed by histology, immunohistochemistry, alpha smooth muscle actin (alpha-SMA) immunoblotting, and quantitative polymerase chain reaction (qPCR).
Ace2 KO mice showed increased liver fibrosis following bile duct ligation for 21 days or chronic carbon tetrachloride (CCl (4)) treatment.
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15362042 Safadi R, Ohta M, Alvarez CE, Fiel MI, Bansal M, Mehal WZ, Friedman SL: Immune stimulation of hepatic fibrogenesis by CD8 cells and attenuation by transgenic interleukin-10 from hepatocytes. Gastroenterology. 2004 Sep;127(3):870-82.

METHODS: We generated transgenic (TG) mice with hepatocyte expression of rat IL-10 (rIL-10) to assess its impact on lymphocyte subsets and activation of hepatic stellate cells following liver injury from carbon tetrachloride (CCl 4 ) or thioacetamide (TAA).
To assess the role of lymphocytes on stellate cell activation, either whole splenic lymphocytes, CD4+, or CD8+ T-cell subsets from WT animals with CCl 4 fibrosis were adoptively transferred to severe combined immunodeficiency (SCID) recipients, which led to stellate cell activation and fibrogenic stimulation as assessed by expression of transforming growth factor (TGF)-beta1 and collagen I messenger RNA (mRNA) and by immunoblot of alpha-smooth muscle actin.
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20106566 Shi H, Dong L, Zhang Y, Bai Y, Zhao J, Zhang L: Protective effect of a coffee preparation (Nescafe pure (R)) against carbon tetrachloride-induced liver fibrosis in rats. Clin Nutr. 2010 Jan 26.

Intragastric administration of a coffee preparation reduced the protein expression of alpha-smooth muscle actin (alpha-SMA) and the glucose-regulated proteins (GRP) 78 and 94 in rats increased by CCl (4).
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20052656 Taura K, Miura K, Iwaisako K, Osterreicher CH, Kodama Y, Penz-Osterreicher M, Brenner DA: Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice. Hepatology. 2010 Mar;51(3):1027-36.

We induced liver fibrosis by repetitive carbon tetrachloride (CCl (4)) injections.
Liver sections and isolated cells were evaluated for GFP and beta-gal as well as expression of alpha-smooth muscle actin (alpha-SMA) and fibroblast-specific protein 1 (FSP-1).
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19475535 Comporti M, Arezzini B, Signorini C, Vecchio D, Gardi C: Oxidative stress, isoprostanes and hepatic fibrosis. . Histol Histopathol. 2009 Jul;24(7):893-900.

Immunocytochemical studies showed the major localization of TxA2r in the perinuclear site and its colocalization with alpha-smooth muscle actin.
In a rat model of carbon tetrachloride-induced hepatic fibrosis, plasma isoprostanes were markedly elevated for the entire experimental period and hepatic collagen content was also increased.
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18263696 Peng Z, Fernandez P, Wilder T, Yee H, Chiriboga L, Chan ES, Cronstein BN: Ecto-5'-nucleotidase (CD73) -mediated extracellular adenosine production plays a critical role in hepatic fibrosis. FASEB J. 2008 Jul;22(7):2263-72. Epub 2008 Feb 8.


There were far fewer alpha-smooth muscle actin positive hepatic stellate cells in CCl (4)-treated KO mice than that in WT mice.
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19910526 Yang JI, Yoon JH, Bang YJ, Lee SH, Lee SM, Byun HJ, Myung SJ, Kim W, Lee HS: Synergistic Anti-Fibrotic Efficacy of Statin and Protein Kinase C Inhibitor in Hepatic Fibrosis. Am J Physiol Gastrointest Liver Physiol. 2009 Nov 12.

Hepatic fibrosis models were established in BALB/c mouse by intraperitoneal injection of carbon tetrachloride or thioacetamide for 6 weeks.
Hepatic fibrosis and HSC activation were assessed by morphometric analysis of histological findings and immunohistochemistry for alpha-smooth muscle actin.
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18634036 Perugorria MJ, Latasa MU, Nicou A, Cartagena-Lirola H, Castillo J, Goni S, Vespasiani-Gentilucci U, Zagami MG, Lotersztajn S, Prieto J, Berasain C, Avila MA: The epidermal growth factor receptor ligand amphiregulin participates in the development of mouse liver fibrosis. Hepatology. 2008 Oct;48(4):1251-61.


We demonstrate that the expression of alpha-smooth muscle actin and collagen deposition were markedly reduced in AR-/- mice compared to AR+/+ animals.
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16652398 Li G, Xie Q, Shi Y, Li D, Zhang M, Jiang S, Zhou H, Lu H, Jin Y: Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats. J Gene Med. 2006 Jul;8(7):889-900.

The number of active hepatic stellate cells (HSCs) determined by the expression of alpha-smooth muscle actin was also significantly decreased.
METHODS: Some rats received carbon tetrachloride (CCl4) by subcutaneous injections every three days for six consecutive weeks, and meantime they also obtained either siRNA (0.1 mg/kg) targeting CTGF, saline or a control siRNA by intraportal vein injection to rats' liver at the same pattern.
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19185565 Dalton SR, Lee SM, King RN, Nanji AA, Kharbanda KK, Casey CA, McVicker BL: Carbon tetrachloride-induced liver damage in asialoglycoprotein receptor-deficient mice. Biochem Pharmacol. 2009 Apr 1;77(7):1283-90. Epub 2009 Jan 13.

The consequences of CCl (4) injection were examined by measuring alpha-smooth muscle actin (alpha-SMA) deposition, contents of malondialdehyde and the percentage of apoptotic hepatocytes.
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20198635 Sobrevals L, Rodriguez C, Romero-Trevejo JL, Gondi G, Monreal I, Paneda A, Juanarena N, Arcelus S, Razquin N, Guembe L, Gonzalez-Aseguinolaza G, Prieto J, Fortes P: Insulin-like growth factor I gene transfer to cirrhotic liver induces fibrolysis and reduces fibrogenesis leading to cirrhosis reversion in rats. Hepatology. 2010 Mar;51(3):912-21.

Rats with liver cirrhosis induced by carbon tetrachloride (CCl (4)) given orally for 8 weeks were injected through the hepatic artery with saline or with Simian virus 40 vectors encoding IGF-I (SVIGF-I), or luciferase (SVLuc).
Rats treated with SVIGF-I showed increased hepatic levels of IGF-I, improved liver function tests, and reduced fibrosis in association with diminished alpha-smooth muscle actin expression, up-regulation of matrix metalloproteases (MMPs) and decreased expression of the tissue inhibitors of MMPs TIM-1 and TIM-2.
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15980055 Fiorucci S, Rizzo G, Antonelli E, Renga B, Mencarelli A, Riccardi L, Morelli A, Pruzanski M, Pellicciari R: Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor gamma contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis. J Pharmacol Exp Ther. 2005 Oct;315(1):58-68. Epub 2005 Jun 24.

Here, we investigated whether FXR ligands regulate PPARgamma expression in HSCs and models of liver fibrosis induced in rats by porcine serum and carbon tetrachloride administration and bile duct ligation.
Cotreatment with 6-ECDCA potentiates the antifibrotic activity of rosiglitazone, a PPARgamma ligand, in the porcine serum model as measured by morphometric analysis of liver collagen content, hydroxyproline, and liver expression of alpha1 (I) collagen mRNA, alpha-smooth muscle actin, fibronectin, TGFbeta1, and tissue inhibitor of metalloprotease 1 and 2, whereas it enhanced the expression of PPARgamma and uncoupling protein 2, a PPARgamma-regulated gene, by 2-fold.
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15052691 Yuan GJ, Zhang ML, Gong ZJ: Effects of PPARg agonist pioglitazone on rat hepatic fibrosis. . World J Gastroenterol. 2004 Apr 1;10(7):1047-51.

METHODS: Rat hepatic fibrosis was induced by carbon tetrachloride (CCl (4)).
Histochemical staining of formalin-fixed liver sections with HE, Masson-Trichrome, and immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA) were performed.
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15876570 Planaguma A, Claria J, Miquel R, Lopez-Parra M, Titos E, Masferrer JL, Arroyo V, Rodes J: The selective cyclooxygenase-2 inhibitor SC-236 reduces liver fibrosis by mechanisms involving non-parenchymal cell apoptosis and PPARgamma activation. FASEB J. 2005 Jul;19(9):1120-2. Epub 2005 May 4.

In this study, we tested the effects of SC-236, a selective cyclooxygenase (COX)-2 inhibitor, in rats with carbon tetrachloride (CCl4)-induced liver fibrosis.
In these animals, SC-236 reduced liver fibrosis as revealed by histological analysis and by a reduction in hepatic hydroxyproline levels, metalloproteinase-2 activity, and alpha-smooth muscle actin expression.
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19136384 Ferre N, Martinez-Clemente M, Lopez-Parra M, Gonzalez-Periz A, Horrillo R, Planaguma A, Camps J, Joven J, Tres A, Guardiola F, Bataller R, Arroyo V, Claria J: Increased susceptibility to exacerbated liver injury in hypercholesterolemic ApoE-deficient mice: potential involvement of oxysterols. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G553-62. Epub 2009 Jan 8.

In this study, apolipoprotein E-deficient (ApoE-/-) mice were evaluated to define potential effects of hypercholesterolemia on the severity of carbon tetrachloride (CCl4)-induced liver injury.
After CCl4 challenge, ApoE-/- mice exhibited exacerbated steatosis (Oil Red O staining), necroinflammation (hematoxylin-eosin staining), macrophage infiltration (F4/80 immunohistochemistry), and fibrosis (Sirius red staining and alpha-smooth muscle actin immunohistochemistry) and more severe liver injury [alanine aminotransferase (ALT) and aspartate aminotransferase] than wild-type controls.
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15651265 Dranoff JA, Kruglov EA, Toure J, Braun N, Zimmermann H, Jain D, Knowles AF, Sevigny J: Ectonucleotidase NTPDase2 is selectively down-regulated in biliary cirrhosis. J Investig Med. 2004 Nov;52(7):475-82.

Confocal immunofluorescence demonstrated a shift of NTPDase2 expression from portal areas to central areas that colocalized with alpha-smooth muscle actin after CCl4 administration.
METHODS: Cirrhosis was induced in experimental rats via BDL and carbon tetrachloride (CCl4) administration.
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16804984 He SX, Luo JY, Wang YP, Wang YL, Fu H, Xu JL, Zhao G, Liu EQ: Effects of extract from Ginkgo biloba on carbon tetrachloride-induced liver injury in rats. World J Gastroenterol. 2006 Jun 28;12(24):3924-8.

Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor beta1 (TGF-beta1), a-smooth muscle actin (alpha-SMA) and type I collagens in liver were determined.
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14739096 Baba S, Fujii H, Hirose T, Yasuchika K, Azuma H, Hoppo T, Naito M, Machimoto T, Ikai I: Commitment of bone marrow cells to hepatic stellate cells in mouse. J Hepatol. 2004 Feb;40(2):255-60.

Upon liver injury, these cells also co-expressed desmin and alpha-smooth muscle actin.
We then examined the histology of liver tissues obtained from BM-transplanted mice with and without carbon tetrachloride-induced injury.
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17030452 Lv P, Luo HS, Zhou XP, Chireyath Paul S, Xiao YJ, Si XM, Liu SQ: Thalidomide prevents rat liver cirrhosis via inhibition of oxidative stress. Pathol Res Pract. 2006;202(11):777-88. Epub 2006 Oct 6.

The cirrhosis of rat was induced by intraperitoneal injection of carbon tetrachloride thrice weekly; meanwhile, thalidomide (10mg/kg or 100mg/kg) was given daily by intragastric administration for 8 weeks.
Immunohistochemistry revealed alpha-smooth muscle actin (alpha-SMA), desmin, and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein in the liver.
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19001734 Yang HX, Yi YR: [Curative effect of interferon-alpha on rat liver fibrosis induced by CCl4]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2008 Oct;33(10):919-25.


Immunohistochemistry was used to detect the expression of Collagen I, alpha-smooth muscle actin (alpha-SMA),and transforming growth factor-beta1 (TGF-beta1) in the rat liver.
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