Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.

Détails

Ressource 1Télécharger: cvw031.pdf (971.84 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_4F5525264BB3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.
Périodique
Cardiovascular Research
Auteur(s)
Crippa S., Nemir M., Ounzain S., Ibberson M., Berthonneche C., Sarre A., Boisset G., Maison D., Harshman K., Xenarios I., Diviani D., Schorderet D., Pedrazzini T.
ISSN
1755-3245 (Electronic)
ISSN-L
0008-6363
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
110
Numéro
1
Pages
73-84
Langue
anglais
Résumé
The adult mammalian heart has poor regenerative capacity. In contrast, the zebrafish heart retains a robust capacity for regeneration into adulthood. These distinct responses are consequences of a differential utilization of evolutionary-conserved gene regulatory networks in the damaged heart. To systematically identify miRNA-dependent networks controlling cardiac repair following injury, we performed comparative gene and miRNA profiling of the cardiac transcriptome in adult mice and zebrafish.
Using an integrated approach, we show that 45 miRNA-dependent networks, involved in critical biological pathways, are differentially modulated in the injured zebrafish vs. mouse hearts. We study, more particularly, the miR-26a-dependent response. Therefore, miR-26a is down-regulated in the fish heart after injury, whereas its expression remains constant in the mouse heart. Targets of miR-26a involve activators of the cell cycle and Ezh2, a component of the polycomb repressive complex 2 (PRC2). Importantly, PRC2 exerts repressive functions on negative regulators of the cell cycle. In cultured neonatal cardiomyocytes, inhibition of miR-26a stimulates, therefore, cardiomyocyte proliferation. Accordingly, miR-26a knockdown prolongs the proliferative window of cardiomyocytes in the post-natal mouse heart.
This novel strategy identifies a series of miRNAs and associated pathways, in particular miR-26a, which represent attractive therapeutic targets for inducing repair in the injured heart.

Mots-clé
Animals, Cell Cycle, Cell Proliferation/genetics, Gene Expression Profiling/methods, Gene Regulatory Networks/genetics, Mice, Inbred C57BL, MicroRNAs/genetics, MicroRNAs/metabolism, Myocytes, Cardiac/physiology, Regeneration, Wound Healing/genetics, Zebrafish
Pubmed
Web of science
Open Access
Oui
Création de la notice
20/02/2016 15:34
Dernière modification de la notice
20/08/2019 14:05
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