期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 120, 期 3, 页码 4573-4581出版社
WILEY
DOI: 10.1002/jcb.27746
关键词
BMP-7; hepatic stellate cells (HSCs); liver fibrosis; miR-542-3p
资金
- National Natural Science Foundation of China [81500469]
- Zhejiang Provincial Natural Science Foundation [LY15H030003]
There has been an increasing number of studies about microRNAs as key regulators in the development of hepatic fibrosis. Here, we demonstrate that miR-542-3p can promote hepatic fibrosis by downregulating the expression of bone morphogenetic protein 7 (BMP-7), which is known to antagonize transforming growth factor beta 1 (TGF beta 1)-mediated fibrogenesis effect. The expression of miR-542-3p is increased in activated hepatic stellate cells (HSCs). Downregulation of MiR-542-3p by antisense inhibitors can inhibit HSCs activation markers, including alpha-smooth muscle actin (alpha-SMA) and collagen as well as TGF beta signaling pathways. MiR-542-3p was significantly upregulated in carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice, and downregulation of miR-542-3p by lentivirus could prevent the development of hepatic fibrosis. In addition, miR-542-3p can directly bind to the 3 '-untranslated region of BMP-7 mRNA, indicating that its profibrotic effect appears to be caused by its inhibition of BMP-7. Our results suggest that downregulation of miR-542-3p prevents liver fibrosis both in vitro and in vivo, highlighting its potential as a novel biomarker or therapeutic target for hepatic fibrosis.
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