CircSMAD3 Represses SMAD3 Phosphorylation and Ameliorates Cardiac Remodeling by Recruiting YBX1

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jul 12

PMID 38993677

Authors

Shuai Mei

Xiaozhu Ma

Li Zhou

Qidamugai Wuyun

Jing Wang

Qianqian Xiao

Man Wang

Kaiyue Zhang

Chen Chen

Jiangtao Yan

Hu Ding

Affiliations

Soon will be listed here.

Abstract

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 . 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.

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