2026-04-29T12:22:47Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/55392024-09-27T09:29:19Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Rodius, Sophie author Nazarov, Petr V. author Nepomuceno-Chamorro, Isabel A. author Jeanty, Celine author Gonzalez-Rosa, Juan Manuel author Ibberson, Mark author da Costa, Ricardo M. Benites author Xenarios, Ioannis author Mercader, Nadia author Azuaje, Francisco author 2014 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. BMC Genomics. 2014; 15(1):852 10.1186/1471-2164-15-852 1471-2164 BMC Genomics http://hdl.handle.net/20.500.12105/5539 Myocardial infarction Zebrafish Ventricular amputation Ventricular cryoinjury Heart regeneration Transcriptional responses Transcriptional association networks INDUCED MYOCARDIAL-INFARCTION HEART REGENERATION NEMALINE MYOPATHY HYPERTROPHIC CARDIOMYOPATHY STEM-CELLS CARDIOVASCULAR-SYSTEM INTERACTION NETWORKS EXPRESSION PROLIFERATION PERIOSTIN Transcriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo models