Molecular regulation of myocardial proliferation and regeneration

Zheng, Lianfang; Du, Jianyong; Wang, Zihao; Zhou, Qinchao; Zhu, Xiaojun; Xiong, Jing-Wei

doi:10.1186/s13619-021-00075-7

Cited by 16 publications

(19 citation statements)

References 202 publications

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“…Persistent loss of CMs following MI can lead to heart failure. The adult mammalian heart only displays a modest regenerative capacity, whereas the heart from early postnatal mice and from adults of lower vertebrates can achieve complete regeneration after ventricular resection by inducing the proliferation of existing CMs [27][28][29]. Therefore, understanding the molecular mechanism underlying reactivation of cell proliferation is essential to induce cardiac regeneration after myocardial injury in adults.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang¹,

Shen

et al. 2023

Preprint

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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 is strongly 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 N6-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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Section: Discussionmentioning

confidence: 99%

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

Zhang¹,

Shen

et al. 2023

Preprint

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“…It is conceivable that cardiomyocyte dedifferentiation and proliferation contribute to heart regeneration in zebrafish 6,7 . Over the past decades, a number of signaling pathways and transcription factors have been reported to regulate myocardial proliferation and regeneration in zebrafish, including fibroblast growth factor, sonic hedgehog, retinoic acid, insulin-like growth factor, Notch, GATA4, Hand2, NF-kB, and Stat3 [8][9][10][11][12][13] . Retinaldehyde dehydrogenase 2, which produces retinoic acid, is activated in the epicardium and endocardium within hours after injury, and transgenic inhibition of retinoic acid receptors impairs myocardial proliferation 8 .…”

Section: Introductionmentioning

confidence: 99%

Endothelial Brg1 fine-tunes Notch signaling during zebrafish heart regeneration

et al. 2023

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Myocardial Brg1 is essential for heart regeneration in zebrafish, but it remains unknown whether and how endothelial Brg1 plays a role in heart regeneration. Here, we found that both brg1 mRNA and protein were induced in cardiac endothelial cells after ventricular resection and endothelium-specific overexpression of dominant-negative Xenopus Brg1 (dn-xbrg1) inhibited myocardial proliferation and heart regeneration and increased cardiac fibrosis. RNA-seq and ChIP-seq analysis revealed that endothelium-specific overexpression of dn-xbrg1 changed the levels of H3K4me3 modifications in the promoter regions of the zebrafish genome and induced abnormal activation of Notch family genes upon injury. Mechanistically, Brg1 interacted with lysine demethylase 7aa (Kdm7aa) to fine-tune the level of H3K4me3 within the promoter regions of Notch family genes and thus regulated notch gene transcription. Together, this work demonstrates that the Brg1-Kdm7aa-Notch axis in cardiac endothelial cells, including the endocardium, regulates myocardial proliferation and regeneration via modulating the H3K4me3 of the notch promoters in zebrafish.

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“…Regeneration neither occurred from one moult to another nor the amputated legs in adults showed regeneration (Wang et al, 2015;Saxena et al, 2016) and was evident only during pupal development. An activation of genes responsible for regeneration probably occurred in pupal stage (Michaud et al, 2020;Zhong et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Limb regeneration is blastema dependent in a ladybird beetle,Cheilomenes sexmaculata(Fabricius)

Rawat,

Rai,

Mishra

2023

Preprint

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Holometabolous insects undergoes metamorphosis which involves an intercalated pupa stage between larva and adult. The body plan of the adult is established during pupa stage and larval systems are de-differentiated and reorganized in insects undergoing complete metamorphosis. In ladybird beetles, the limbs amputated in the larval stages are regenerated in the adults. This occurs during pupation. Given that changes in the pupa are akin to embryogenesis, does the lost limbs are redeveloped as a part of metamorphosis or has some pre-patterning initiated prior pupation? To study this we hypothesised that limb regeneration in a holometabolous ladybird beetles,Cheilomenes sexmaculatais the result of the recapitulation of the embryonic gene programs in the pupa. To test this, we exposed the third larval stages ofCheilomenes sexmaculata(Fabricius) to amputation and prior to amputation the tissues on the amputated site was scraped off every 24hrs. It was found that limb regeneration does not occur in the treatment where scrapping was done. Assuming that these epidermal cells correspond to blastema, for limb regeneration in ladybird beetles blastema is essential and does not occur in its absence.

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Molecular regulation of myocardial proliferation and regeneration

Cited by 16 publications

References 202 publications

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

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

Endothelial Brg1 fine-tunes Notch signaling during zebrafish heart regeneration

Limb regeneration is blastema dependent in a ladybird beetle,Cheilomenes sexmaculata(Fabricius)

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