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000299003 041__ $$aEnglish
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000299003 1001_ $$aGupta, Savita$$b0
000299003 245__ $$aThe transmembrane glycoprotein Gpnmb is required for the immune and fibrotic responses during zebrafish heart regeneration.
000299003 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2025
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000299003 520__ $$aMyocardial infarction occurs when the coronary supply of oxygen and nutrients to part of the heart is interrupted. In contrast to adult mammals, adult zebrafish have a remarkable ability to regenerate their heart after cardiac injury. Several processes are involved in this regenerative response including inflammation, coronary endothelial cell proliferation and revascularization, endocardial expansion, cardiomyocyte repopulation, and transient scar formation. To identify additional regulators of zebrafish cardiac regeneration, we profiled the transcriptome of regenerating coronary endothelial cells at 7 days post cryoinjury (dpci) and observed the significant upregulation of dozens of genes including gpnmb. Gpnmb (glycoprotein non-metastatic melanoma protein B) is a transmembrane glycoprotein implicated in inflammation resolution and tissue regeneration. Transcriptomic profiling data of cryoinjured zebrafish hearts reveal that gpnmb is mostly expressed by macrophages. To investigate gpnmb function during zebrafish cardiac regeneration, we generated a full locus deletion allele. We find that after cardiac cryoinjury, animals lacking gpnmb exhibit neutrophil retention and decreased macrophage recruitment as well as reduced myofibroblast numbers. Moreover, loss of gpnmb impairs coronary endothelial cell regeneration and cardiomyocyte dedifferentiation. Transcriptomic analyses of cryoinjured gpnmb-/- hearts identified enhanced collagen gene expression and the activation of extracellular matrix (ECM) related pathways. Furthermore, gpnmb-/- hearts exhibit larger fibrotic scars revealing additional defects in cardiac regeneration. Altogether, these data indicate that gpnmb, which is mostly expressed by macrophages, modulates inflammation and ECM deposition after cardiac cryoinjury in zebrafish and further highlight the importance of these immune cells during regeneration.
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000299003 650_7 $$2Other$$aZebrafish
000299003 650_7 $$2Other$$acardiac regeneration
000299003 650_7 $$2Other$$acoronary
000299003 650_7 $$2Other$$agpnmb
000299003 650_7 $$2Other$$amacrophages
000299003 7001_ $$aBajwa, Gursimran Kaur$$b1
000299003 7001_ $$0P:(DE-He78)1c7746e47f511c0b4e5ef0bb2b0fbd49$$aEl-Sammak, Hadil$$b2$$udkfz
000299003 7001_ $$aMattonet, Kenny$$b3
000299003 7001_ $$aGünther, Stefan$$b4
000299003 7001_ $$aLooso, Mario$$b5
000299003 7001_ $$aStainier, Didier Y R$$b6
000299003 7001_ $$aMarín-Juez, Rubén$$b7
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