miR-142-3p Is a Regulator of the TGFβ-Mediated Vascular Smooth Muscle Cell Phenotype

J Cell Biochem. 2015 Oct;116(10):2325-33. doi: 10.1002/jcb.25183.

Abstract

The transforming growth factor β (TGFβ) signaling pathway is critical for the promotion and maintenance of the contractile phenotype of vascular smooth muscle cells (VSMCs). Though multiple microRNAs (miRNAs) implicated in the regulation of the VSMC phenotype have been identified, the modulation of miRNAs in the VSMCs by TGFβ signaling has not been fully described. In this study, we identified microRNA-142-3p (miR-142-3p) as a modulator of the VSMC phenotype in response to TGFβ signaling. We show that miR-142-3p is induced upon TGFβ signaling, leading to the repression of a novel target, dedicator of cytokinesis 6 (DOCK6). The downregulation of DOCK6 by miR-142-3p is critical for cell migration. Thus, this study demonstrates that miR-142-3p is a key regulator of the TGFβ-mediated contractile phenotype of VSMCs that acts through inhibiting cell migration through targeting DOCK6.

Keywords: DOCK6; MICRORNA-142-3p; TGFβ; VASCULAR SMOOTH MUSCLE CELLS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation / drug effects
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / metabolism*
  • Phenotype
  • Pulmonary Artery / cytology
  • Pulmonary Artery / metabolism
  • Recombinant Proteins
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / metabolism

Substances

  • DOCK6 protein, human
  • Guanine Nucleotide Exchange Factors
  • MIRN142 microRNA, human
  • MicroRNAs
  • Recombinant Proteins
  • Transforming Growth Factor beta