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

Cell Reports
Jean Z LinStephen R Farmer

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.

Citations

Dec 21, 2018·Obesity·Suzanne N Shapira, Patrick Seale
Feb 13, 2020·Scientific Reports·Jessica E C JonesStephen R Farmer
Oct 5, 2018·JCI Insight·Ritwik DattaKamran Atabai
Sep 10, 2019·The Journal of Clinical Investigation·Geneviève MarcelinKarine Clément
Aug 8, 2020·Frontiers in Cell and Developmental Biology·Iryna PyrinaAntonios Chatzigeorgiou
Jun 10, 2021·Reviews in Endocrine & Metabolic Disorders·Geneviève Marcelin, Karine Clément
Nov 4, 2021·Scientific Reports·Golnaz Anvari, Evangelia Bellas
Jan 16, 2022·Cell Stem Cell·Jitske JansenRafael Kramann

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