期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms13498
关键词
-
资金
- National Natural Science Foundation of China [81330079, 81273569, 81401292, 81670553, 81373466, 91313303, 81422050, 91129728]
- Natural Science Foundation of Jiangsu Province [BK20140614]
Excessive activation of hepatic stellate cells (HSCs) is a key step in liver fibrogenesis. Here we report that CUG-binding protein 1 (CUGBP1) expression is elevated in HSCs and positively correlates with liver fibrosis severity in human liver biopsies. Transforming growth factor-beta (TGF-beta) selectively increases CUGBP1 expression in cultured HSCs in a p38 mitogen-activated protein kinase (MAPK)-dependent manner. Knockdown of CUGBP1 inhibits alpha smooth muscle actin (alpha-SMA) expression and promotes interferon gamma (IFN-gamma) production in HSCs in vitro. We further show that CUGBP1 specifically binds to the 3' untranslated region (UTR) of human IFN-gamma mRNA and promotes its decay. In mice, knockdown of CUGBP1 alleviates, whereas its overexpression exacerbates, bile duct ligation (BDL)-induced hepatic fibrosis. Therefore, CUGBP1-mediated IFN-gamma mRNA decay is a key event for profibrotic TGF-beta-dependent activation of HSCs, and inhibiting CUGBP1 to promote IFN-gamma signalling in activated HSCs could be a novel strategy to treat liver fibrosis.
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