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Chen TF, Chen M, Qin JH, Wang MY: [Interventional effects of emodin on transforming growth factor-beta1/integrin-linked kinase signal way in interleukin-1beta-induced transdifferentiation of rat tubular epithelial-myofibroblasts]. J Refract Surg. 2008 Nov;24(9):923-7. OBJECTIVE: To study the effects of transforming growth factor-beta1/integrin-linked kinase (TGF-beta1/ILK) signal way in interleukin-1beta (IL-1beta)-induced rat tubular epithelial-myofibroblast transdifferentiation (TEMT), and to investigate whether emodin inhibits IL-1beta-induced TEMT through the TGF-beta1/ILK signal way-dependent mechanism. METHODS: Normal rat kidney epithelial cell line (NRK52E) was used in this study. NRK52E cells were divided into blank control group, emodin control group, IL-1beta-induced group, emodin-inhibited group, SB431542 (TGF-beta 1 type I receptor blocker)-inhibited group, emodin plus SB431542-inhibited group, emodin-pretreated group and emodin-reversed group. After 48-hour culture, morphological changes of the NRK52E cells were observed by an inverted phase contrast microscope. The expressions of alpha-smooth muscle actin (alpha-SMA) and E-cadherin were detected by two-color immunohistochemical staining, while the expressions of TGF-beta1 and ILK were detected by one-color immunohistochemical staining. We also performed the imaging analysis to quantitatively analyze the result of the immunohistochemical staining. The secretion of fibronectin (FN) was analyzed by enzyme-linked immunosorbent assay. RESULTS: Compared with the blank control group, IL-1beta might induce TEMT, which was showed in increasing expression of alpha-SMA, increasing secreting of FN and decreasing expression of E-cadherin, and at the same time the expressions of TGF-beta1 and ILK were enhanced (P <0.05). Emodin might inhibit all of those changes induced by IL-1beta (P <0.05). When TGF-beta1 signal way was intercepted, IL-1beta induced-TEMT was suppressed and the expression of ILK was decreased, however, there was no significant difference in expression of TGF-beta1 between the SB431542 group and the IL-1beta-induced group. Compared with emodin-inhibited group, emodin-pretreatment could not prevent IL-1beta induced-TEMT in a certain extent, but emodin could not revert IL-1beta-induced TEMT. Spearman correlation analysis showed that TGF-beta1 expression had positive correlation with expressions of alpha-SMA, FN, ILK and negative correlation with E-cadherin expression, and the expression of ILK was positively correlated with the expressions of alpha-SMA and FN and negatively correlated with E-cadherin expression. CONCLUSION: IL-1beta induces TEMT partly depending on TGF-beta1/ILK signal way, partly via which emodin inhibits the TEMT induced by IL-1beta. |
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