Myocardin-Related Transcription Factor A Promotes Recruitment of ITGA5+ Profibrotic Progenitors during Obesity-Induced Adipose Tissue Fibrosis

Cell Rep. 2018 May 15;23(7):1977-1987. doi: 10.1016/j.celrep.2018.04.057.

Abstract

Adipose tissue fibrosis is associated with inflammation and insulin resistance in human obesity. In particular, visceral fat fibrosis is correlated with hyperlipidemia and ectopic fat accumulation. Myocardin-related transcription factor A (MRTFA) is an important coactivator that mediates the transcription of extracellular matrix and other fibrogenic genes. Here, we examine the role of MRTFA in the development of adipose tissue fibrosis and identify a signaling pathway that regulates the fate of vascular progenitors. We demonstrate that obesity induces the formation of Sca1-, Sma+, ITGA5+ fibrogenic progenitor cells (FPCs) in adipose tissue. MRTFA deficiency in mice shifts the fate of perivascular progenitors from FPCs to adipocyte precursor cells and protects against chronic obesity-induced fibrosis and accompanying metabolic dysfunction, without a shift in energy expenditure. Our findings highlight the ITGA5-MRTFA pathway as a potential target to ameliorate obesity-associated metabolic disease.

Keywords: adipose tissue fibrosis; integrin; myocardin-related transcription factor; progenitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipose Tissue / pathology*
  • Animals
  • Cell Differentiation
  • Chronic Disease
  • Energy Metabolism
  • Fatty Liver / pathology
  • Fibrosis
  • Hypertrophy
  • Inflammation / pathology
  • Insulin Resistance
  • Integrin alpha5 / metabolism*
  • Mice, Inbred C57BL
  • Models, Biological
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology
  • Obesity / pathology*
  • Stem Cells / metabolism*
  • Trans-Activators / deficiency
  • Trans-Activators / metabolism*
  • Transforming Growth Factor beta / metabolism

Substances

  • Integrin alpha5
  • Mrtfa protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta