Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression

Exp Mol Pathol. 2014 Dec;97(3):542-9. doi: 10.1016/j.yexmp.2014.11.002. Epub 2014 Nov 6.

Abstract

Objective: The aim of the present work was to investigate the mechanism of transforming growth factor (TGF)-β1 and Sloan-Kettering Institute (Ski) in the pathogenesis of hypertrophic scars (HS).

Background: Wound healing is an inherent process, but the aberrant wound healing of skin injury may lead to HS. There has been growing evidence suggesting a role for TGF-β1 and Ski in the pathogenesis of fibrosis.

Material and methods: The MTT assay was used to detect the cell proliferation induced by TGF-β1. The Ski gene was transduced into cells with an adenovirus, and then the function of Ski in cell proliferation and differentiation was observed. Ski mRNA levels were measured by RT-PCR. Western blotting was used to detect the protein expression of α-SMA, E-cadherin, Meox1, Meox2, Zeb1 and Zeb2.

Results: TGF-β1 can promote human skin fibroblast (HSF) cell proliferation in a time-dependent manner, but the promoting effect could be suppressed by Ski. TGF-β1 also induces the formation of the myofibroblast phenotype and the effect of TGF-β1 could be diminished by Ski. Also, Ski modulates the cardiac myofibroblast phenotype and function through suppression of Zeb2 by up-regulating the expression of Meox2.

Conclusions: Ski diminishes the myofibroblast phenotype induced by TGF-β1 through the suppression of Zeb2 by up-regulating the expression of Meox2.

Keywords: Expression of Meox2; Ski; TGF-β1.

Publication types

  • Retracted Publication

MeSH terms

  • Blotting, Western
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Cicatrix, Hypertrophic / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Homeodomain Proteins / metabolism*
  • Humans
  • Myofibroblasts / cytology
  • Myofibroblasts / metabolism*
  • Phenotype
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation
  • Wound Healing / physiology

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • MEOX2 protein, human
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Transforming Growth Factor beta1
  • SKI protein, human