Format

Send to

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

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

Author information

1
Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
2
Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA. Electronic address: sfarmer@bu.edu.

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

PMID:
29768198
DOI:
10.1016/j.celrep.2018.04.057
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center