Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in the acute inflammatory phase after myocardial infarction.
Does Dusp6 deficiency attenuate neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction in animal models?
DUSP6 deficiency attenuates neutrophil-mediated cardiac damage post-MI, suggesting DUSP6 as a potential therapeutic target for post-MI cardiac remodeling.
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.
Zhou et al. (Sat,) conducted a other in Myocardial infarction. Dusp6 deficiency vs. Wild-type controls was evaluated on Cardiac function and infarct size. Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in the acute inflammatory phase after myocardial infarction.