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bioRxiv · 10.1101/2021.01.29.428781

Midkine-a regulates the formation of a fibrotic scar during zebrafish heart regeneration

Grivas, D.·Gonzalez-Rajal, A.·de la Pompa, J. L.
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Abstract

The adult zebrafish heart regenerates after injury, unlike the hearts of mammals. Heart cryoinjury 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 is strongly induced at 1-day post cryoinjury (dpci) throughout the epicardium, whereas by 7 dpci expression has become restricted to 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 a blockade of heart regeneration characterized by retention of a collagenous scar. Transcriptional analysis revealed increases in collagen transcription and TGF{beta} signalling activity. These results reveal a critical role for mdka in fibrosis regulation during heart regeneration.

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Grivas, D., Gonzalez-Rajal, A., de la Pompa, J. L.. 2021-01-31. Midkine-a regulates the formation of a fibrotic scar during zebrafish heart regeneration. https://doi.org/10.1101/2021.01.29.428781

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