The Function And Mechanisms Of DUSP26 In Pathological Cardiac Hypertrophy

Background:Cardiac pathological hypertrophy is closely related to major adverse cardiovascular events such as arrhythmia and heart failure,which also leads to sudden cardiac death.Dual-specificity phosphatase 26(DUSP26)belongs to the dual-specificity phosphatase family,which has a significant effect on nonalcoholic fatty liver disease,neuroblastoma,glioma,and so on.However,the involvement of DUSP26 in cardiac hypertrophy has not been reported.Methods and results:Our study showed that in mouse hearts in response to pressure overload as well as in angiotensin ?—treated cardiomyocytes,the expression of DUSP26 increased obviously.Cardiac-specific overexpression of DUSP26 mice showed attenuated cardiac hypertrophy and fibrosis,while deficiency of DUSP26 in mouse hearts resulted in increased cardiac hypertrophy and deteriorated cardiac function.Similar effects were also observed in cellular hypertrophy induced by angiotensin ?.Importantly,we showed that DUSP26 bound to TAK1 and inhibited its phosphorylation,which led to suppression of the MAPK signaling pathway.In addition,TAK1-specific inhibitor inhibited cardiomyocyte hypertrophy induced by angiotensin ? and attenuated the exaggerated hypertrophic response in DUSP26 conditional knockout mice.Conclusions:Taken together,DUSP26 was induced in cardiac hypertrophy and protected against pressure overload induced cardiac hypertrophy by modulating TAK1-p38/JNKsignaling axis.