MicroRNA-942 mediates hepatic stellate cell activation by regulating BAMBI expression in human liver fibrosis.
Arch Toxicol
; 92(9): 2935-2946, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30097701
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-ß) 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-ß signaling and also partly mediates LPS-induced proinflammatory HSC fate. In conclusion, the TGF-ß 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Células Estreladas do Fígado
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Cirrose Hepática
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Revista:
Arch Toxicol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China