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
Citation
Grivas, D., González-Rajal, Á., de la Pompa, J.L. (2021) Midkine-a Regulates the Formation of a Fibrotic Scar During Zebrafish Heart Regeneration. Frontiers in cell and developmental biology. 9:669439.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping