MeCP2 promotes endothelial-to-mesenchymal transition in human endothelial cells by downregulating BMP7 expression

Exp Cell Res. 2019 Feb 1;375(1):82-89. doi: 10.1016/j.yexcr.2018.12.020. Epub 2018 Dec 28.

Abstract

Endothelial-to-mesenchymal transition (EndMT) plays a pivotal role in the development of organ fibrosis and can be induced by TGF-β. It is characterized by the loss of endothelial cell markers and the acquisition of mesenchymal markers. In this study, we found that methyl-CpG binding protein 2 (MeCP2) was increased in TGF-β-induced EndMT, and silencing of MeCP2 inhibited EndMT induction. Viral overexpression of MeCP2 in vitro promoted EndMT and suppressed the expression of bone morphogenic protein-7 (BMP7). The methylation of CpG islands in BMP7 promoter was increased in MeCP2-overexpressing endothelial cells and Chromatin immunoprecipitation assay showed the direct binding of MeCP2 at the BMP7 promoter. In summary, our results suggest that MeCP2 promotes EndMT by epigenetically silencing BMP7 in endothelial cells and MeCP2 may be a target for diseases driven by EndMT.

Keywords: BMP7; DNA methylation; Endothelial-mesenchymal transition; Epigenetic; MeCP2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 7 / genetics*
  • Cell Movement / genetics
  • DNA Methylation / genetics
  • DNA-Binding Proteins / genetics
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Epigenesis, Genetic / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Fibrosis / genetics*
  • Fibrosis / pathology
  • Gene Expression Regulation / genetics
  • Gene Silencing
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Promoter Regions, Genetic / genetics
  • Transforming Growth Factor beta / genetics

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • DNA-Binding Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Transforming Growth Factor beta