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@ARTICLE{Gupta:299003,
author = {S. Gupta and G. K. Bajwa and H. El-Sammak$^*$ and K.
Mattonet and S. Günther and M. Looso and D. Y. R. Stainier
and R. Marín-Juez},
title = {{T}he transmembrane glycoprotein {G}pnmb is required for
the immune and fibrotic responses during zebrafish heart
regeneration.},
journal = {Developmental biology},
volume = {521},
issn = {0012-1606},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2025-00413},
pages = {153-162},
year = {2025},
note = {2025 May;521:153-162},
abstract = {Myocardial 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.},
keywords = {Zebrafish (Other) / cardiac regeneration (Other) / coronary
(Other) / gpnmb (Other) / macrophages (Other)},
cin = {A290},
ddc = {570},
cid = {I:(DE-He78)A290-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39983908},
doi = {10.1016/j.ydbio.2025.02.011},
url = {https://inrepo02.dkfz.de/record/299003},
}