한빛사논문
- 조회340
성균관대학교 의과대학
Byeong-Yun Ahn 1,3, Yan Zhang 1,3, Shibo Wei 1,3, Yideul Jeong 2, Dong-Hyun Park 1, Sang-Jin Lee 2, Young-Eun Leem 1,* and Jong-Sun Kang 1,*
1Department of Molecular Cell Biology, Sungkyunkwan University, School of Medicine, Suwon, Republic of Korea.
2Research Institute of Aging-Related Diseases, AniMusCure, Inc, Suwon, Republic of Korea.
3These authors contributed equally: Byeong-Yun Ahn, Yan Zhang, Shibo Wei.
*Corresponding authors: correspondence to Young-Eun Leem or Jong-Sun Kang
Abstract
Protein arginine methyltransferases (PRMTs) modulate diverse cellular processes, including stress responses. The present study explored the role of Prmt7 in protecting against menopause-associated cardiomyopathy. Mice with cardiac-specific Prmt7 ablation (cKO) exhibited sex-specific cardiomyopathy. Male cKO mice exhibited impaired cardiac function, myocardial hypertrophy, and interstitial fibrosis associated with increased oxidative stress. Interestingly, female cKO mice predominantly exhibited comparable phenotypes only after menopause or ovariectomy (OVX). Prmt7 inhibition in cardiomyocytes exacerbated doxorubicin (DOX)-induced oxidative stress and DNA double-strand breaks, along with apoptosis-related protein expression. Treatment with 17β-estradiol (E2) attenuated the DOX-induced decrease in Prmt7 expression in cardiomyocytes, and Prmt7 depletion abrogated the protective effect of E2 against DOX-induced cardiotoxicity. Transcriptome analysis of ovariectomized wild-type (WT) or cKO hearts and mechanical analysis of Prmt7-deficient cardiomyocytes demonstrated that Prmt7 is required for the control of the JAK/STAT signaling pathway by regulating the expression of suppressor of cytokine signaling 3 (Socs3), which is a negative feedback inhibitor of the JAK/STAT signaling pathway. These data indicate that Prmt7 has a sex-specific cardioprotective effect by regulating the JAK/STAT signaling pathway and, ultimately, may be a potential therapeutic tool for heart failure treatment depending on sex.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-03-15)
- 국내 연구진
- 의약학 > 분자세포의학
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