期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 332, 期 3, 页码 747-754出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.109.162727
关键词
-
资金
- National Science Foundation of China [30730030]
- Program for New Century Excellent Talents in University
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 (CCl4) but increased in that induced by bile duct ligation (BDL). Therefore, we examined whether A(1)AR contributes to hepatic fibrosis in CCl4 and BDL animal models using A(1)AR knockout mice. Compared with wild-type (WT) mice, hepatic fibrosis resulting from chronic CCl4 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. Hepa-tocyte damage was reduced in A(1)AR(-/-) mice after a single injection of CCl4, with down-regulation of CYP2E1 and UCP2 gene expression in livers, which resulted in impaired liver sensitivity to CCl4. 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. CCl4 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据