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

Publication date: 15 May 2018
Source:Cell Reports, Volume 23, Issue 7
Author(s): Jean Z. Lin, Nabil Rabhi, Stephen R. Farmer
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.

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Teaser

Identification of signaling pathways regulating obesity-induced adipose tissue fibrosis has therapeutic potential. Lin et al. show that myocardin-related transcription factor A (MRTFA) drives the recruitment of fibrogenic progenitor cells (FPCs) at the expense of healthy adipocytes. MRTFA-deficient mice are protected from chronic diet-induced obesity and fibrosis without a change in energy expenditure.


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