Critical role of Lin28-TNFR2 signalling in cardiac stem cell activation and differentiation.
J Cell Mol Med
; 23(4): 0, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30734494
ABSTRACT
Tumour necrotic factor receptor-2 (TNFR2) has been to be cardiac-protective and is expressed in cardiac progenitor cells. Our goal is to define the mechanism for TNFR2-mediated cardiac stem cell activation and differentiation. By employing a protocol of in vitro cardiac stem cell (CSC) differentiation from human inducible pluripotent stem cell (hiPSC), we show that expression of TNFR2 precedes expression of CSC markers followed by expression of mature cardiomyocyte proteins. Activation of TNFR2 by a specific agonist promotes whereas inhibition of TNFR2 by neutralizing antibody diminishes hiPSC-based CSC differentiation. Interestingly, pluripotent cell factor RNA-binding protein Lin28 enhances TNFR2 protein expression in early CSC activation by directly binding to a conserved Lin28-motif within the 3'UTR of Tnfr2 mRNA. Furthermore, inhibition of Lin28 blunts TNFR2 expression and TNFR2-dependent CSC activation and differentiation. Our study demonstrates a critical role of Lin28-TNFR2 axis in CSC activation and survival, providing a novel strategy to enhance stem cell-based therapy for the ischaemic heart diseases.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Proteínas de Ligação a RNA
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Miócitos Cardíacos
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Receptores Tipo II do Fator de Necrose Tumoral
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Células-Tronco Pluripotentes Induzidas
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Células-Tronco Embrionárias Humanas
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China