Myocardin-Related Transcription Factor A Promotes Recruitment of ITGA5+ Profibrotic Progenitors during Obesity-Induced Adipose Tissue Fibrosis.
Cell Rep
; 23(7): 1977-1987, 2018 05 15.
Article
em En
| MEDLINE
| ID: mdl-29768198
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Transativadores
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Tecido Adiposo
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Integrina alfa5
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Obesidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article