PUBLICATION
The transmembrane glycoprotein Gpnmb is required for the immune and fibrotic responses during zebrafish heart regeneration
- Authors
- Gupta, S., Bajwa, G.K., El-Sammak, H., Mattonet, K., Günther, S., Looso, M., Stainier, D.Y.R., Marín-Juez, R.
- ID
- ZDB-PUB-250222-4
- Date
- 2025
- Source
- Developmental Biology : (Journal)
- Registered Authors
- Stainier, Didier
- Keywords
- Zebrafish, cardiac regeneration, coronary, gpnmb, macrophages
- MeSH Terms
-
- Endothelial Cells/metabolism
- Regeneration*
- Neutrophils/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Macrophages/metabolism
- Animals
- Myocardium/metabolism
- Myocardium/pathology
- Transcriptome/genetics
- Gene Expression Profiling
- Zebrafish*/metabolism
- Myocytes, Cardiac/metabolism
- Membrane Glycoproteins*/genetics
- Membrane Glycoproteins*/metabolism
- Inflammation/metabolism
- Heart*
- Fibrosis*/metabolism
- PubMed
- 39983908 Full text @ Dev. Biol.
Citation
Gupta, S., Bajwa, G.K., El-Sammak, H., Mattonet, K., Günther, S., Looso, M., Stainier, D.Y.R., Marín-Juez, R. (2025) The transmembrane glycoprotein Gpnmb is required for the immune and fibrotic responses during zebrafish heart regeneration. Developmental Biology. :.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping