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oai:repisalud.isciii.es:20.500.12105/153802024-09-27T08:50:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Grivas, Dimitrios author González-Rajal, Álvaro author de la Pompa, José Luis author 2021 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 TGFβ signaling activity. These results reveal a critical role for mdka in fibrosis regulation during heart regeneration. Cell Dev Biol. 2021 May 7;9:669439 10.3389/fcell.2021.669439 2296-634X Frontiers in cell and developmental biology 34026760 http://hdl.handle.net/20.500.12105/15380 Midkine-a Regulates the Formation of a Fibrotic Scar During Zebrafish Heart Regeneration.