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Midkine-a Regulates the Formation of a Fibrotic Scar During Zebrafish Heart Regeneration


Unlike the hearts of mammals, the adult zebrafish heart regenerates after injury. Heart cryoinjury in zebrafish triggers the formation of a fibrotic scar that gradually degrades, leading to regeneration. Midkine-a (Mdka) is a multifunctional cytokine that is activated after cardiac injury. Here, we investigated the role of mdka in zebrafish heart regeneration. We show that mdka expression was induced at 1-day post-cryoinjury (dpci) throughout the epicardial layer, whereas by 7 dpci expression had become restricted to the epicardial cells covering the injured area. To study the role of mdka in heart regeneration, we generated mdka-knock out (KO) zebrafish strains. Analysis of injured hearts showed that loss of mdka decreased endothelial cell proliferation and resulted in an arrest in heart regeneration characterized by retention of a collagenous scar. Transcriptional analysis revealed increases in collagen transcription and intense TGFbeta signaling activity. These results reveal a critical role for mdka in fibrosis regulation during heart regeneration.

Type Journal
ISBN 2296-634X (Print) 2296-634X (Linking)
Authors Grivas, D.; Gonzalez-Rajal, A.; de la Pompa, J. L.
Responsible Garvan Author Dr Alvaro Gonzalez Rajal
Publisher Name Frontiers in Cell and Developmental Biology
Published Date 2021-05-31
Published Volume 9
Published Pages 669439
Status Published in-print
DOI 10.3389/fcell.2021.669439
URL link to publisher's version