IGF2BP3 promotes adult myocardial regeneration by stabilizing MMP3 mRNA through interaction with m6A modification - Sorbonne Université
Article Dans Une Revue Cell Death Discovery Année : 2023

IGF2BP3 promotes adult myocardial regeneration by stabilizing MMP3 mRNA through interaction with m6A modification

Simeng Li
  • Fonction : Auteur
Siman Shen
  • Fonction : Auteur
Hao Xu
  • Fonction : Auteur
Shuyun Cai
  • Fonction : Auteur
Xiaodong Yuan
  • Fonction : Auteur
Changsen Wang
  • Fonction : Auteur
Xiaojun Zhang
  • Fonction : Auteur
Suyun Chen
  • Fonction : Auteur
Jianning Chen
  • Fonction : Auteur
Liangqing Zhang

Résumé

Myocardial infarction that causes damage to heart muscle can lead to heart failure. The identification of molecular mechanisms promoting myocardial regeneration represents a promising strategy to improve cardiac function. Here we show that IGF2BP3 plays an important role in regulating adult cardiomyocyte proliferation and regeneration in a mouse model of myocardial infarction. IGF2BP3 expression progressively decreases during postnatal development and becomes undetectable in the adult heart. However, it becomes upregulated after cardiac injury. Both gain-and loss-of-function analyses indicate that IGF2BP3 regulates cardiomyocyte proliferation in vitro and in vivo. In particular, IGF2BP3 promotes cardiac regeneration and improves cardiac function after myocardial infarction. Mechanistically, we demonstrate that IGF2BP3 binds to and stabilizes MMP3 mRNA through interaction with N 6-methyladenosine modification. The expression of MMP3 protein is also progressively downregulated during postnatal development. Functional analyses indicate that MMP3 acts downstream of IGF2BP3 to regulate cardiomyocyte proliferation. These results suggest that IGF2BP3-mediated post-transcriptional regulation of extracellular matrix and tissue remodeling contributes to cardiomyocyte regeneration. They should help to define therapeutic strategy for ameliorating myocardial infarction by inducing cell proliferation and heart repair.
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hal-04100169 , version 1 (17-05-2023)

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Simeng Li, Siman Shen, Hao Xu, Shuyun Cai, Xiaodong Yuan, et al.. IGF2BP3 promotes adult myocardial regeneration by stabilizing MMP3 mRNA through interaction with m6A modification. Cell Death Discovery, 2023, 9 (164), ⟨10.1038/s41420-023-01457-3⟩. ⟨hal-04100169⟩
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