PUBLICATION
Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction
- Authors
- Zhou, X., Zhang, C., Wu, X., Hu, X., Zhang, Y., Wang, X., Zheng, L., Gao, P., Du, J., Zheng, W., Shang, H., Hu, K., Jiang, Z., Nie, Y., Hu, S., Xiao, R.P., Zhu, X., Xiong, J.W.
- ID
- ZDB-PUB-221107-1
- Date
- 2022
- Source
- Nature communications 13: 6672 (Journal)
- Registered Authors
- Xiong, Jing-Wei
- Keywords
- none
- MeSH Terms
-
- Animals
- Dual Specificity Phosphatase 6
- Mice
- Mice, Knockout
- Myocardial Infarction*/genetics
- Myocardium
- Myocytes, Cardiac
- Neutrophils
- Rats
- PubMed
- 36335128 Full text @ Nat. Commun.
Citation
Zhou, X., Zhang, C., Wu, X., Hu, X., Zhang, Y., Wang, X., Zheng, L., Gao, P., Du, J., Zheng, W., Shang, H., Hu, K., Jiang, Z., Nie, Y., Hu, S., Xiao, R.P., Zhu, X., Xiong, J.W. (2022) Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction. Nature communications. 13:6672.
Abstract
Dual-specificity phosphatase 6 (DUSP6) serves a specific and conserved function on the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). We previously identified Dusp6 as a regenerative repressor during zebrafish heart regeneration, therefore we propose to investigate the role of this repressor in mammalian cardiac repair. Utilizing a rat strain harboring Dusp6 nonsense mutation, rat neutrophil-cardiomyocyte co-culture, bone marrow transplanted rats and neutrophil-specific Dusp6 knockout mice, we find that Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in acute inflammatory phase after myocardial infarction. Mechanistically, Dusp6 is transcriptionally activated by p38-C/EBPβ signaling and acts as an effector for maintaining p-p38 activity by down-regulating pERK and p38-targeting phosphatases DUSP1/DUSP16. Our findings provide robust animal models and novel insights for neutrophil-mediated cardiac damage and demonstrate the potential of DUSP6 as a therapeutic target for post-MI cardiac remodeling and other relevant inflammatory diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping