PUBLICATION

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

Authors
Grivas, D., González-Rajal, Á., de la Pompa, J.L.
ID
ZDB-PUB-210525-9
Date
2021
Source
Frontiers in cell and developmental biology   9: 669439 (Journal)
Registered Authors
de la Pompa, José Luis, Grivas, Dimitrios
Keywords
Midkine-a, collagen, epicardium, fibrotic scar, signaling/signaling pathways, zebrafish heart regeneration
Datasets
GEO:GSE166732
MeSH Terms
none
PubMed
34026760 Full text @ Front Cell Dev Biol
Abstract
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.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cn105
    Indel
    li1TgTransgenic Insertion
      y1TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        mdkaCRISPR2-mdkaCRISPR
        1 - 1 of 1
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        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-aldh1a2polyclonalIgGRabbit
        Ab1-mdkapolyclonalRabbit
        Ab1-mef2polyclonal
          IgGRabbit
          Ab2-smad3monoclonal
            IgGRabbit
            1 - 4 of 4
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            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            EGFPEFGEGFP
            1 - 1 of 1
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            Mapping
            No data available