Dynamic expression of miR-126* and its effects on proliferation and contraction of hepatic stellate cells

FEBS Lett. 2013 Nov 29;587(23):3792-801. doi: 10.1016/j.febslet.2013.09.047. Epub 2013 Oct 16.

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: 3′UTR; 3′untranslated region; Akt; COL IV; Chronic liver disease; ECM; EGFL7; GO; HA; HE; HSC; Hepatic stellate cell; KEGG; LN; PCIII; PI3K; Portal hypertension; VEGF; VEGFA; VG; Van Gieson; epidermal growth factor-1ike domain 7; extracellular matrix; gene ontology; hematoxylin/eosin; hepatic stellate cell; hyalaronic acid; kyoto encyclopedia of genes and genomes; laminin; miR-126(∗); miRNA; microRNA; phosphatidylinositol-3-kinase; procollagen typeIII; protein kinase B; type IV collagen; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation*
  • Extracellular Matrix / metabolism
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / physiology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Transcription, Genetic
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • MIRN126 microRNA, rat
  • MicroRNAs
  • Vascular Endothelial Growth Factor A