| First Author | Liu J | Year | 2022 |
| Journal | J Cardiovasc Transl Res | Volume | 15 |
| Issue | 6 | Pages | 1219-1238 |
| PubMed ID | 35596107 | Mgi Jnum | J:334132 |
| Mgi Id | MGI:7446849 | Doi | 10.1007/s12265-022-10268-3 |
| Citation | Liu J, et al. (2022) Dual Specific Phosphatase 7 Exacerbates Dilated Cardiomyopathy, Heart Failure, and Cardiac Death by Inactivating the ERK1/2 Signaling Pathway. J Cardiovasc Transl Res 15(6):1219-1238 |
| abstractText | 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. |
