Participation of miR-200a in TGF-β1-mediated hepatic stellate cell activation

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• 作者：Xu Sun (1) (2)
  Yong He (1) (2)
  Tao-Tao Ma (1) (2)
  Cheng Huang (1) (2)
  Lei Zhang (1) (2)
  Jun Li (1) (2)
  
• 关键词：miR ; 200a ; Hepatic stellate cells ; TGF ; β ; α ; SMA ; β ; Catenin
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2014
• 出版时间：March 2014
• 年：2014
• 卷：388
• 期：1-2
• 页码：11-23
• 全文大小：775 KB
• 作者单位：Xu Sun (1) (2)
  Yong He (1) (2)
  Tao-Tao Ma (1) (2)
  Cheng Huang (1) (2)
  Lei Zhang (1) (2)
  Jun Li (1) (2)
  
  1. School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Mei Shan Road, Hefei, 230032, Anhui Province, People’s Republic of China
  2. The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, People’s Republic of China
  
• ISSN：1573-4919

文摘

Hepatic stellate cell (HSC) activation is a pivotal event in the initiation and progression of hepatic fibrosis since it mediates transforming growth factor beta 1 (TGF-β1)-driven extracellular matrix (ECM) deposition. MicroRNAs (miRNAs), small non-coding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key factors to regulate cell proliferation, differentiation, and apoptosis. Although the function of miR-200a has been discussed in many cancers and fibrotic diseases, its role in hepatic fibrosis is still poorly understood. The aim of this study is to investigate whether miR-200a could attenuate hepatic fibrosis partly through Wnt/β-catenin and TGF-β-dependant mechanisms. Our study found that the expression of endogenous miR-200a was decreased in vitro in TGF-β1-induced HSC activation as well as in vivo in CCl4-induced rat liver fibrosis. Overexpression of miR-200a significantly inhibited α-SMA activity and further affected the proliferation of TGF-β1-dependent activation of HSC. In addition, we identified β-catenin and TGF-β2 as two functional downstream targets for miR-200a. Interestingly, miR-200a specifically suppressed β-catenin in the protein level, whereas miR-200a-mediated suppression of TGF-β2 was shown on both mRNA and protein levels. Our results revealed the critical regulatory role of miR-200a in HSC activation and implied miR-200a as a potential candidate for therapy by deregulation of Wnt/β-catenin and TGFβ signaling pathways, at least in part, via decreasing the expression of β-catenin and TGF-β2.