Activation of hepatic stellate cells is suppressed by microRNA-150

• Published in: International journal of molecular medicine Vol. 32; no. 1; pp. 17 - 24
• Main Authors: ZHENG, JIANJIAN, LIN, ZHUO, DONG, PEIHONG, LU, ZHONGQIU, GAO, SHENMENG, CHEN, XIAOQIAN, WU, CUNZAO, YU, FUJUN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-07-2013; Spandidos Publications UK Ltd
• Subjects: Cell growth; Cell Line; Cluster Analysis; Collagen; Collagen Type IV - genetics; Dose-Response Relationship, Drug; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; hepatic stellate cells; Hepatic Stellate Cells - metabolism; Hepatitis; Humans; Liver diseases; liver fibrosis; Medical prognosis; microRNA-150; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Phosphorylation; Polyclonal antibodies; Protein expression; Proteins; RNA Interference; Sp1 Transcription Factor - genetics; Transforming Growth Factor beta1 - pharmacology; United States > US
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2013.1356

microRNAs (miRNAs) have recently been reported to be involved in the progression of liver fibrosis. It has previously been shown that miR-150 can inhibit the activation of hepatic stellate cells (HSCs) via the inhibition of C-myb expression. However, the reduced C-myb expression is not responsible for all the effects of miR-150, there may be other molecular mechanisms for the suppression of HSCs by miR-150. In this study, gene array analysis was performed to analyze the miRNAs that were differentially expressed between LX-2 cells induced by transforming growth factor-β1 (TGF-β1) and the control. Our results indicated that the expression of miR-150 was significantly reduced during liver fibrosis. Of note, the reduction of miR-150 induced by TGF-β1 was in a dose- and time-dependent manner. In addition, miR-150 overexpression in LX-2 cells resulted in the inhibition of cell proliferation and the reduction of extracellular matrix proteins and α-smooth muscle actin (α-SMA). However, there was no significant change in the rate of apoptosis in cells transfected with miR-150 mimics compared with the control. Sp1, a mediator of α-1 (I) collagen (Col1A1) expression, and Col4A4 were found to be the targets for miR-150. Also, miR-150 mimics were found to decrease the expression of Sp1 and Col4A4. Smad2 and p-Smad2, the upstream mediators of Sp1, were not affected by miR-150. The same result was also seen in the levels of Smad3 and p-Smad3. Collectively, we conclude that miR-150 can reduce type I and IV collagen by directly binding to Sp1 and Col4A4 without the involvement of upstream of the TGF-β/Smad pathway.