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

BMC Genomics

Francisco Azuaje⁵  Nadia Mercader⁸  Ioannis Xenarios⁷  Ricardo M Benites da Costa²  Mark Ibberson⁶  Juan Manuel González-Rosa⁴  Céline Jeanty⁵  Isabel A Nepomuceno-Chamorro¹  Petr V Nazarov³  Sophie Rodius⁵ 

[1] Departamento Lenguajes y Sistemas Informáticos, Universidad de Sevilla, Seville, Spain;Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland;Genomics Research Unit, CRP-Santé, Luxembourg, Luxembourg;Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, USA;NorLux Neuro-Oncology Laboratory, CRP-Santé, Luxembourg, Luxembourg;Vital-IT Systems Biology/Medicine Department, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland;Department of Biochemistry, University of Geneva, Geneva, Switzerland;Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares Carlos III, CNIC, Madrid, Spain

关键词: Transcriptional association networks;    Transcriptional responses;    Heart regeneration;    Ventricular cryoinjury;    Ventricular amputation;    Zebrafish;    Myocardial infarction;   

Others  :  1139151
DOI  :  10.1186/1471-2164-15-852

 received in 2014-09-15, accepted in 2014-09-25,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Rodius et al.; licensee BioMed Central Ltd.

【 图 表 】

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