Activation of hepatic stellate cells is suppressed by microRNA-150

Zheng,Jianjian; Lin,Zhuo; Dong,Peihong; Lu,Zhongqiu; Gao,Shenmeng; Chen,Xiaoqian; Wu,Cunzao; Yu,Fujun

doi:10.3892/ijmm.2013.1356

Activation of hepatic stellate cells is suppressed by microRNA-150

Authors:
- Jianjian Zheng
- Zhuo Lin
- Peihong Dong
- Zhongqiu Lu
- Shenmeng Gao
- Xiaoqian Chen
- Cunzao Wu
- Fujun Yu
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Affiliations: Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Emergency Department, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Laboratory of Nephrology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Institute of Organ Transplantation, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China
Published online on: April 22, 2013 https://doi.org/10.3892/ijmm.2013.1356
Pages: 17-24

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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.

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