Antiinflammatory activity of ANGPTL4 facilitates macrophage polarization to induce cardiac repair.
JCI Insight
; 4(16)2019 08 22.
Article
em En
| MEDLINE
| ID: mdl-31434807
ABSTRACT
Mesenchymal stem cells (MSCs) can suppress pathological inflammation. However, the mechanisms underlying the association between MSCs and inflammation remain unclear. Under coculture conditions with macrophages, MSCs highly expressed angiopoietin-like 4 (ANGPTL4) to blunt the polarization of macrophages toward the proinflammatory phenotype. ANGPTL4-deficient MSCs failed to inhibit the inflammatory macrophage phenotype. In inflammation-related animal models, the injection of coculture medium or ANGPTL4 protein increased the antiinflammatory macrophages in both peritonitis and myocardial infarction. In particular, cardiac function and pathology were markedly improved by ANGPTL4 treatment. We found that retinoic acid-related orphan receptor α (RORα) was increased by inflammatory mediators, such as IL-1ß, and bound to ANGPTL4 promoter in MSCs. Collectively, RORα-mediated ANGPTL4 induction was shown to contribute to the antiinflammatory activity of MSCs against macrophages under pathological conditions. This study suggests that the capability of ANGPTL4 to induce tissue repair is a promising opportunity for safe stem cell-free regeneration therapy from a translational perspective.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peritonite
/
Células-Tronco Mesenquimais
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Proteína 4 Semelhante a Angiopoietina
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Ativação de Macrófagos
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Macrófagos
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Infarto do Miocárdio
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2019
Tipo de documento:
Article