| 20007753 |
Yang P, Han Z, Chen P, Zhu L, Wang S, Hua Z, Zhang J: A contradictory role of A1 adenosine receptor in carbon tetrachloride- and bile duct ligation-induced liver fibrosis in mice. J Pharmacol Exp Ther. 2010 Mar;332(3):747-54. Epub 2009 Dec 10.
Mice lacking A (1) adenosine receptors (A (1) AR) were thought to be protected from developing fatty liver; however, the contribution of A (1) AR to hepatic fibrosis has not been explored. Here we found that the expression of A (1) AR was decreased in fibrotic liver induced by chronic carbon tetrachloride (CCl (4)) but increased in that induced by bile duct ligation (BDL). Therefore, we examined whether A (1) AR contributes to hepatic fibrosis in CCl (4) and BDL animal models using A (1) AR knockout mice. Compared with wild-type (WT) mice, hepatic fibrosis resulting from chronic CCl (4) exposure was attenuated in A (1) AR (-/-) mice with markedly decreased collagen deposition and reduced hepatic stellate cell activation, whereas bile duct-ligated A (1) AR (-/-) mice displayed a significant increase in hepatic fibrosis. Hepatocyte damage was reduced in A (1) AR (-/-) mice after a single injection of CCl (4), with down-regulation of CYP2E1 and UCP2 gene expression in livers, which resulted in impaired liver sensitivity to CCl (4). However, BDL caused severe bile infarcts in livers of A (1) AR (-/-) mice, with significantly elevated levels of bile acid compared with those in WT mice. CCl (4) and BDL resulted in different expression patterns of genes involved in fibrogenesis in A (1) AR (-/-) mice. These results indicate that A (1) AR participates in the pathogenesis of hepatic fibrosis with a complex mechanism, and the effect of targeting adenosine and its receptors in the prevention of hepatic fibrosis should be cautiously evaluated. |
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