title: Activation of hepatic stellate cells is suppressed by microRNA-150.
abstract: 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.
authors.affiliation: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Zheng
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Lin
authors.forename: Peihong
authors.initials: P
authors.lastname: Dong
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Lu
authors.forename: Shenmeng
authors.initials: S
authors.lastname: Gao
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Chen
authors.forename: Cunzao
authors.initials: C
authors.lastname: Wu
authors.forename: Fujun
authors.initials: F
authors.lastname: Yu
mesh_terms: D002460:Cell Line; D016000:Cluster Analysis; D024141:Collagen Type IV / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D016329:Sp1 Transcription Factor / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D024141:Collagen Type IV; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D053773:Transforming Growth Factor beta1; C466620:COL4A4 protein, human; C533097:MIR150, human