MicroRNA-942 mediates hepatic stellate cell activation by regulating BAMBI expression in human liver fibrosis.
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-beta) and lipopolyssacharide (LPS), two major drivers of liver fibrosis and inflammation, induce miR-942 expression in HSCs via Smad2/3 respective NF-kappaB/p50 binding to the miR-942 promoter. Mechanistically, the induced miR-942 degrades BAMBI mRNA in HSCs, thereby sensitizing the cells for fibrogenic TGF-beta signaling and also partly mediates LPS-induced proinflammatory HSC fate. In conclusion, the TGF-beta 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.
SEEK ID: https://seek.lisym.org/publications/150
PubMed ID: 30097701
Projects: LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Fail..., LiSyM network
Publication type: Not specified
Journal: Arch Toxicol
Citation: Arch Toxicol. 2018 Sep;92(9):2935-2946. doi: 10.1007/s00204-018-2278-9. Epub 2018 Aug 10.
Date Published: 12th Aug 2018
Registered Mode: Not specified
Views: 3157
Created: 14th Jan 2019 at 13:27
Last updated: 8th Mar 2024 at 07:44
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