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. 2022 Dec;15(6):1219-1238.
doi: 10.1007/s12265-022-10268-3. Epub 2022 May 20.

Dual Specific Phosphatase 7 Exacerbates Dilated Cardiomyopathy, Heart Failure, and Cardiac Death by Inactivating the ERK1/2 Signaling Pathway

Jing Liu  1 , Yihen Yin  1   2 , Jing Ni  1 , Peiyu Zhang  1 , Wei-Ming Li  3   4 , Zheng Liu  5   6   7
Affiliations

Dual Specific Phosphatase 7 Exacerbates Dilated Cardiomyopathy, Heart Failure, and Cardiac Death by Inactivating the ERK1/2 Signaling Pathway

Jing Liu et al. J Cardiovasc Transl Res. 2022 Dec.

Abstract

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.

Keywords: Dilated cardiomyopathy; Dual specific phosphatase 7; ERK1/2 signaling pathway; Heart failure.

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