Lefty1 Ameliorates Post-infarction Fibrosis by Suppressing p-Smad2 and p-ERK1/2 Signaling Pathways.
J Cardiovasc Transl Res
; 14(4): 636-646, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33409963
ABSTRACT
Transforming growth factor-ß1 signaling pathways are known to involve in the development of post-infarction fibrosis, a process characterized by the aberrant activation, proliferation, and differentiation of fibroblasts, as well as the unbalanced turnover of extracellular matrix proteins. Recent studies have shown that Lefty1, a novel member of TGF-ß superfamily, acts as a brake on the TGF-ß signaling pathway in non-cardiac tissues. However, its role in myocardial infarction (MI)-induced fibrosis and left ventricular remodeling has not been fully elucidated. Here, for the first time, we reported that Lefty1 alleviated post-MI fibroblast proliferation, differentiation, and secretion through suppressing p-Smad2 and p-ERK1/2 signaling pathways in vivo and in vitro. In MI mice or TGF-ß1-treated neonatal rat cardiac fibroblasts (CFBs), the expression of Lefty1 was upregulated. Adenovirus-mediated overexpression of Lefty1 significantly attenuated TGF-ß1-induced CFBs' proliferation, differentiation, and collagen production. Using the adeno-associated virus approach, we confirmed that Lefty1 attenuates MI-induced cardiac injury, as evidenced by the decreased infarct size and preserved cardiac function. These results highlight the importance of Lefty1 in the prevention of post-MI fibrosis and may help identify potential targets for therapeutic intervention of cardiac fibrosis. Graphical abstract.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase 1 Ativada por Mitógeno
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Miócitos Cardíacos
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Proteína Quinase 3 Ativada por Mitógeno
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Proteína Smad2
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Fatores de Determinação Direita-Esquerda
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Infarto do Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article