Liver fibrosis causes downregulation of miRNA-150 and miRNA-194 in hepatic stellate cells, and their overexpression causes decreased stellate cell activation
Open Access
- 1 January 2010
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 298 (1), G101-G106
- https://doi.org/10.1152/ajpgi.00220.2009
Abstract
Activation of hepatic stellate cells (HSC) results in their proliferation and in the secretion of extracellular matrix (ECM) proteins, which leads to hepatic fibrosis. microRNAs (miRNAs) have been shown to regulate various cell functions, such as proliferation, differentiation, and apoptosis. Hence, we have analyzed the miRNAs that were differentially expressed in HSC isolated from sham-operated and bile duct-ligated rats. Expression of two miRNAs, miRNA-150 and miRNA-194, was reduced in HSC isolated from fibrotic rats compared with sham-operated animals. These two miRNAs were overexpressed in LX-2 cells, and their ability to inhibit cell proliferation, the expression of smooth muscle α-actin (SMA), a marker for activation, and collagen type I, a marker for ECM secretion, was determined. Overexpression of these two miRNAs resulted in a significant inhibition of proliferation ( P < 0.05) and reduced SMA and collagen I levels compared with either untreated cells or nonspecific miRNA-expressing cells. Next, the protein targets of these two miRNAs were found using bioinformatics approaches. C-myb was found to be a target for miRNA-150, and rac 1 was found to be one of the targets for miRNA-194. Therefore, we studied the expression of these two proteins by overexpressing these two miRNAs in LX-2 cells and found that overexpression of miRNA-150 and miRNA-194 resulted in a significant inhibition of c-myb and rac 1 expression, respectively. We conclude that both miRNA-150 and miRNA-194 inhibit HSC activation and ECM production, at least in part, via inhibition of c-myb and rac 1 expression.Keywords
This publication has 26 references indexed in Scilit:
- The microRNA-30 Family Is Required for Vertebrate Hepatobiliary DevelopmentGastroenterology, 2009
- Over‐expressed microRNA‐27a and 27b influence fat accumulation and cell proliferation during rat hepatic stellate cell activationFEBS Letters, 2009
- microRNA-122 stimulates translation of hepatitis C virus RNAThe EMBO Journal, 2008
- Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expressionHepatology, 2008
- c-Myb Is an Evolutionary Conserved miR-150 Target and miR-150/c-Myb Interaction Is Important for Embryonic DevelopmentMolecular Biology and Evolution, 2008
- Leptin induces phagocytosis of apoptotic bodies by hepatic stellate cells via a Rho guanosine triphosphatase-dependent mechanismHepatology, 2008
- Recent advances in the pathogenesis and diagnosis of liver fibrosisThe Esophagus, 2008
- Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in miceHepatology, 2006
- The functions of animal microRNAsNature, 2004
- Hepatic expression of c-Myb in chronic human liver diseaseHepatology, 1997