PUBLICATION
Nr4a1 modulates inflammation and heart regeneration in zebrafish
- Authors
- Feng, D., Dong, Y., Song, Y., Yapundich, N., Xie, Y., Spurlock, B., Lyu, T., Kuehn, L., Qian, L., Liu, J.
- ID
- ZDB-PUB-250625-11
- Date
- 2025
- Source
- Development (Cambridge, England) : (Journal)
- Registered Authors
- Liu, Jiandong
- Keywords
- Cardiac regeneration, Macrophage, Neutrophil, Nr4a1
- Datasets
- GEO:GSE276850
- MeSH Terms
-
- Inflammation*/genetics
- Inflammation*/metabolism
- Fibrosis
- Nuclear Receptor Subfamily 4, Group A, Member 1*/genetics
- Nuclear Receptor Subfamily 4, Group A, Member 1*/metabolism
- Regeneration*/genetics
- Regeneration*/physiology
- Animals
- Neutrophils/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Heart*/physiology
- Zebrafish*/genetics
- Zebrafish*/physiology
- PubMed
- 40554763 Full text @ Development
Citation
Feng, D., Dong, Y., Song, Y., Yapundich, N., Xie, Y., Spurlock, B., Lyu, T., Kuehn, L., Qian, L., Liu, J. (2025) Nr4a1 modulates inflammation and heart regeneration in zebrafish. Development (Cambridge, England). :.
Abstract
Recent findings have highlighted the complex role of inflammation in zebrafish heart regeneration, demonstrating that while inflammation is essential for initiating transient fibrosis and tissue repair, chronic inflammation, and unresolved fibrosis could impede full regenerative recovery. In this study, we identified the nuclear receptor Nr4a1 as a critical regulator of this regenerative process in zebrafish. Loss of Nr4a1 function led to a prolonged and excessive inflammatory response, disrupted neutrophil migration, delayed fibrin clearance, and ultimately impaired heart regeneration. Transcriptome-wide RNA-seq analysis at different injury stages revealed molecular disruptions associated with dysregulated inflammation and fibrosis in Nr4a1 mutants. Notably, partial inhibition of the pro-inflammatory cytokine Tnf-α rescued heart regeneration in the nr4a1 mutants, highlighting the therapeutic potential of modulating inflammation. Our findings suggest that Nr4a1 plays a crucial role in orchestrating the immune response during heart regeneration and may serve as a valuable target for enhancing cardiac repair following injury.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping