PUBLICATION
Attenuation of epicardial activation and myofibroblast abundance via the Fbln2-Nupr1b axis stimulates cardiac regeneration in zebrafish
- Authors
- Kayman Kürekçi, G., Kaur Bajwa, G., Zhang, S., Leclerc, S., de Chantal, E., Belke, D., Andelfinger, G., Deniset, J.F., Marín-Juez, R.
- ID
- ZDB-PUB-260304-8
- Date
- 2026
- Source
- Nature cardiovascular research : (Journal)
- Registered Authors
- Kayman Kürekçi, Gülsüm, Marín-Juez, Rubén
- Keywords
- none
- Datasets
- GEO:GSE294073
- MeSH Terms
- none
- PubMed
- 41776059 Full text @ Nat Cardiovasc Res
Citation
Kayman Kürekçi, G., Kaur Bajwa, G., Zhang, S., Leclerc, S., de Chantal, E., Belke, D., Andelfinger, G., Deniset, J.F., Marín-Juez, R. (2026) Attenuation of epicardial activation and myofibroblast abundance via the Fbln2-Nupr1b axis stimulates cardiac regeneration in zebrafish. Nature cardiovascular research. :.
Abstract
After injury, the adult human heart fails to regenerate and forms a persistent fibrotic scar. By contrast, fibrosis is transient in the injured zebrafish heart, facilitating cell recruitment and providing regenerative cues. The mechanisms that restrain excessive fibrosis while enabling regeneration remain poorly understood. Here we show that fibulin-2 (Fbln2) regulates specific populations of activated epicardial cells to balance the response to cardiac injury. Using genetic tools for Fbln2 dosage, we find that attenuation of epicardial activation stimulates regenerative programs. Mechanistically, we identify epicardial nuclear protein 1b (Nupr1b) as an Fbln2 effector. Using gain- and loss-of-function approaches, we show that Nupr1b controls epicardial myofibroblast abundance. Notably, epicardial-specific overexpression of nupr1b rescued fbln2 mutant phenotypes. These findings shed light on how modulation of epicardial cell state transitions through Fbln2-Nupr1b signaling regulates regenerative responses after cardiac injury.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping