Transcriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo models.

Détails

Ressource 1Télécharger: BIB_093534C78CCD.P001.pdf (1470.51 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_093534C78CCD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Transcriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo models.
Périodique
BMC Genomics
Auteur(s)
Rodius S., Nazarov P.V., Nepomuceno-Chamorro I.A., Jeanty C., González-Rosa J.M., Ibberson M., da Costa R.M., Xenarios I., Mercader N., Azuaje F.
ISSN
1471-2164 (Electronic)
ISSN-L
1471-2164
Statut éditorial
Publié
Date de publication
2014
Volume
15
Numéro
1
Pages
852
Langue
anglais
Résumé
BACKGROUND: Zebrafish is a clinically-relevant model of heart regeneration. Unlike mammals, it has a remarkable heart repair capacity after injury, and promises novel translational applications. Amputation and cryoinjury models are key research tools for understanding injury response and regeneration in vivo. An understanding of the transcriptional responses following injury is needed to identify key players of heart tissue repair, as well as potential targets for boosting this property in humans.
RESULTS: We investigated amputation and cryoinjury in vivo models of heart damage in the zebrafish through unbiased, integrative analyses of independent molecular datasets. To detect genes with potential biological roles, we derived computational prediction models with microarray data from heart amputation experiments. We focused on a top-ranked set of genes highly activated in the early post-injury stage, whose activity was further verified in independent microarray datasets. Next, we performed independent validations of expression responses with qPCR in a cryoinjury model. Across in vivo models, the top candidates showed highly concordant responses at 1 and 3 days post-injury, which highlights the predictive power of our analysis strategies and the possible biological relevance of these genes. Top candidates are significantly involved in cell fate specification and differentiation, and include heart failure markers such as periostin, as well as potential new targets for heart regeneration. For example, ptgis and ca2 were overexpressed, while usp2a, a regulator of the p53 pathway, was down-regulated in our in vivo models. Interestingly, a high activity of ptgis and ca2 has been previously observed in failing hearts from rats and humans.
CONCLUSIONS: We identified genes with potential critical roles in the response to cardiac damage in the zebrafish. Their transcriptional activities are reproducible in different in vivo models of cardiac injury.
Mots-clé
Myocardial infarction, Zebrafish, Ventricular amputation, Ventricular cryoinjury, Heart regeneration, Transcriptional responses, Transcriptional association networks
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/11/2014 9:25
Dernière modification de la notice
20/08/2019 12:31
Données d'usage