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- Title
MicroRNA-942 mediates hepatic stellate cell activation by regulating BAMBI expression in human liver fibrosis.
- Authors
Tao, Le; Xue, Dongying; Shen, Dongxiao; Ma, Wenting; Zhang, Jie; Wang, Xuefei; Zhang, Wei; Wu, Liu; Pan, Kai; Yang, Yanqin; Nwosu, Zeribe C.; Dooley, Steven; Seki, Ekihiro; Liu, Cheng
- Abstract
MicroRNA (miRNA)-mediated gene regulation contributes to liver pathophysiology, including hepatic stellate cell (HSC) activation and fibrosis progression. Here, we investigated the role of miR-942 in human liver fibrosis. The expression of miR-942, HSC activation markers, transforming growth factor-beta pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI), as well as collagen deposition, were investigated in 100 liver specimens from patients with varying degree of hepatitis B virus (HBV)-related fibrosis. Human primary HSCs and the immortalized cell line (LX2 cells) were used for functional studies. We found that miR-942 expression was upregulated in activated HSCs and correlated inversely with BAMBI expression in liver fibrosis progression. Transforming growth factor beta (TGF-β) and lipopolyssacharide (LPS), two major drivers of liver fibrosis and inflammation, induce miR-942 expression in HSCs via Smad2/3 respective NF-κB/p50 binding to the miR-942 promoter. Mechanistically, the induced miR-942 degrades BAMBI mRNA in HSCs, thereby sensitizing the cells for fibrogenic TGF-β signaling and also partly mediates LPS-induced proinflammatory HSC fate. In conclusion, the TGF-β and LPS-induced miR-942 mediates HSC activation through downregulation of BAMBI in human liver fibrosis. Our study provides new insights on the molecular mechanism of HSC activation and fibrosis.
- Subjects
MICRORNA; PATHOLOGICAL physiology; FIBROSIS; CELL lines; HEPATITIS B virus
- Publication
Archives of Toxicology, 2018, Vol 92, Issue 9, p2935
- ISSN
0340-5761
- Publication type
Article
- DOI
10.1007/s00204-018-2278-9