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Dynamic expression of miR-126 and its effects on proliferation and contraction of hepatic stellate cells
Authors:Can-Jie Guo  Qin Pan  Hua Xiong  Yu-Qi Qiao  Zhao-Lian Bian  Wei Zhong  Li Sheng  Hai Li  Lei Shen  Jing Hua  Xiong Ma  Jing-Yuan Fang
Affiliation:1. Digestive Disease Laboratory and Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200001, China;2. Digestive Disease Laboratory and Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China
Abstract:In our previous study, miR-126 was identified as one of the leading miRNAs that is downregulated during activation of hepatic stellate cells (HSCs). However, the roles and related mechanisms of miR-126 in HSCs are not understood. In this study, we compared expression of miR-126 during HSC activation both in vitro and in vivo. We also applied RNA interference to analyze the role and mechanism of miR-126 in the activation of HSCs. Restoring HSCs with Lv-miR-126 resulted in decreased proliferation, accumulation of extracellular matrix components, and cell contraction, while also negatively regulating the vascular endothelial growth factor (VEGF) signal transduction pathways by partially targeted VEGF-A. Thus, we postulate that miR-126 may be a biological marker for the activation of HSCs, and useful for reducing intrahepatic vascular resistance and improving the sinusoidal microcirculation in chronic liver diseases.
Keywords:miRNA, microRNA   HSC, hepatic stellate cell   VEGF, vascular endothelial growth factor   GO, gene ontology   KEGG, kyoto encyclopedia of genes and genomes   VG, Van Gieson   ECM, extracellular matrix   3&prime  UTR, 3&prime  untranslated region   HE, hematoxylin/eosin   PI3K, phosphatidylinositol-3-kinase   Akt, protein kinase B   EGFL7, epidermal growth factor-1ike domain 7   HA, hyalaronic acid   LN, laminin   PCIII, procollagen typeIII   COL IV, type IV collagen
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