CircSMAD3 represses SMAD3 phosphorylation and ameliorates cardiac remodeling by recruiting YBX1

Shuai Mei; Xiaozhu Ma; Li Zhou; Qidamugai Wuyun; Jing Wang; Qianqian Xiao; Man Wang; Kaiyue Zhang; Chen Chen; Jiangtao Yan; Hu Ding

iScience (Jul 2024)

CircSMAD3 represses SMAD3 phosphorylation and ameliorates cardiac remodeling by recruiting YBX1

Shuai Mei,
Xiaozhu Ma,
Li Zhou,
Qidamugai Wuyun,
Jing Wang,
Qianqian Xiao,
Man Wang,
Kaiyue Zhang,
Chen Chen,
Jiangtao Yan,
Hu Ding

Affiliations

Shuai Mei: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Xiaozhu Ma: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Li Zhou: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Qidamugai Wuyun: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Jing Wang: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Qianqian Xiao: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Man Wang: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Kaiyue Zhang: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Chen Chen: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China
Jiangtao Yan: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China; Corresponding author
Hu Ding: Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China; Corresponding author

Journal volume & issue: Vol. 27, no. 7
p. 110200

Abstract

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Summary: Circular RNA (circRNA) has emerged as potential therapeutic targets for cardiovascular diseases. Given the central role of the TGFβ signaling pathway in cardiac remodeling and its potential as a therapeutic target, we hypothesized that a circRNA from this pathway could modulate cardiac remodeling and serve as a heart failure treatment. Therefore, we identified a circRNA, named circSMAD3, that was significantly reduced in murine heart failure models. Functionally, circSMAD3 mitigated cardiomyocyte hypertrophy and inhibited cardiac fibroblast activation in vitro. Mechanistically, circSMAD3 interacts with YBX1, stabilizing it and facilitating its binding to SMAD3 in the nucleus, disrupting the TGFβ/SMAD3 signaling pathway, and ultimately restoring cardiac remodeling. This study highlights circSMAD3 as a promising therapeutic target for heart failure treatment.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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