Dual Specific Phosphatase 7 Exacerbates Dilated Cardiomyopathy, Heart Failure, and Cardiac Death by Inactivating the ERK1/2 Signaling Pathway
Dual Specific Phosphatase 7 Exacerbates Dilated Cardiomyopathy, Heart Failure, and Cardiac Death by Inactivating the ERK1/2 Signaling Pathway
复制标题
双特异性磷酸酶 7 通过灭活 ERK1/2 信号通路加剧扩张型心肌病、心力衰竭和心源性死亡
DOI：
10.1007/s12265-022-10268-3
复制
发表时间：
2022-05-20
影响因子：
3.4
通讯作者：
Liu，Zheng
中科院分区：
文献类型：
--
作者：
Liu，Jing;Yin，Yihen;Liu，Zheng
Heart failure is one of the most common but complicated end-stage syndromes in clinical practice. Dilated cardiomyopathy is a myocardial structural abnormality that is associated with heart failure. Dual-specificity phosphatases (DUSPs) are a group of protein phosphatases that regulate signaling pathways in numerous diseases; however, their physiological and pathological impact on cardiovascular disease remains unknown. In the present study, we generated two transgenic mouse models, a DUSP7 knockout and a cardiac-specific DUSP7 overexpressor. Mice overexpressing DUSP7 showed an exacerbated disease phenotype, including severe dilated cardiomyopathy, heart failure, and cardiac death. We further demonstrated that high levels of DUSP7 inhibited ERK1/2 phosphorylation and influenced downstream c-MYC, c-FOS, and c-JUN gene expression but did not affect upstream activators. Taken together, our study reveals a novel molecular mechanism for DUSP7 and provides a new therapeutic target and clinical path to alleviate dilated cardiomyopathy and improve cardiac function.Graphical abstract
