Unmusking of Protein Phosphatase 2 Regulatory Subunit B as a crucial factor in the development and progression of dilated cardiomyopathy-Reference-Cited by-同舟云学术

Unmusking of Protein Phosphatase 2 Regulatory Subunit B as a crucial factor in the development and progression of dilated cardiomyopathy

Published:2023-09-20 Issue: Volume: Page:
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Author:

Peng Luying¹,Li Li,Fan Huimin²,Lin Fang¹,Liang Xiaoting³,Zhu Yuping¹,Meng Yilei¹,Zhou Xiaohui⁴,Yi Na¹,Lin Qin¹,Hu Sangyu¹,Sheng Jie¹,He Siyu¹,Sachinidis Agapios⁵^ORCID

Affiliation:

1. Tongji University

2. Clinical Translational Medical Research Center

3. The University of Hong Kong

4. Shanghai East Hospital,Tongji University School of Medicine,No.150 Jimo Rd., Shanghai 200120, P.R. China.

5. University of Cologne

Abstract

Abstract Dilated cardiomyopathy (DCM) is one of the major causes of heart failure (HF). However, although significant progress was made in elucidating the underlying mechanisms, the actual therapeutic efforts are inefficient. Here we investigated the potential role of Ppp2r5d, a protein phosphatase 2A (PP2A) regulatory subunit for the development of DCM. We observed that the mRNA level of Ppp2r5d mRNA level was decreased and upregulated in the plasma of DCM patients. Knockdown of Ppp2r5d in murine cardiomyocytes increased the intracellular reactive oxygen species (ROS) levels and reduced ATP synthesis. In a mouse experimental DCM model, heart-specific Ppp2r5d knockdown aggravated the pathogenesis of DCM and induced HF. Mechanistically, Ppp2r5d-deficient cardiomyocytes indicated an elevation of the phosphorylation of Stat3 at the Y705 site, leading to the upregulation of hypertrophic genes such as Anp and Bnp and interleukin 6 (IL6). In parallel, Ppp2r5d-deficient cardiomyocytes indicated a decreased phosphorylation level of Stat3 at S727, an impaired mitochondrial electron transport chain, ATP synthesis and impaired ROS levels. Therefore, our results revealed a novel role of Ppp2r5d in regulating the phosphorylation of Stat3 in the heart, Ppp2r5d might be a potential target for preventing DCM.

Publisher

Research Square Platform LLC

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