Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis

Cai-Xia Ma, Zhi-Ru Wei, Tong Sun, Ming-Hui Yang, Yu-Qie Sun, Kun-Lun Kai, Jia-Chen Shi, Meng-Jiao Zhou, Zi-Wei Wang, Jing Chen, Wei Li, Tian-Qi Wang, Shan-Feng Zhang, Lixiang Xue, Min Zhang, Qianqian Yin, Ming-Xi Zang

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1 Citation (Scopus)


The transdifferentiation from cardiac fibroblasts to myofibroblasts is an important event in the initiation of cardiac fibrosis. However, the underlying mechanism is not fully understood. Circ-sh3rf3 (circular RNA SH3 domain containing Ring Finger 3) is a novel circular RNA which was induced in hypertrophied ventricles by isoproterenol hydrochloride, and our work has established that it is a potential regulator in cardiac hypertrophy, but whether circ-sh3rf3 plays a role in cardiac fibrosis remains unclear, especially in the conversion of cardiac fibroblasts into myofibroblasts. Here, we found that circ-sh3rf3 was down-regulated in isoproterenol-treated rat cardiac fibroblasts and cardiomyocytes as well as during fibroblast differentiation into myofibroblasts. We further confirmed that circ-sh3rf3 could interact with GATA-4 proteins and reduce the expression of GATA-4, which in turn abolishes GATA-4 repression of miR-29a expression and thus up-regulates miR-29a expression, thereby inhibiting fibroblast-myofibroblast differentiation and myocardial fibrosis. Our work has established a novel Circ-sh3rf3/GATA-4/miR-29a regulatory cascade in fibroblast-myofibroblast differentiation and myocardial fibrosis, which provides a new therapeutic target for myocardial fibrosis.

Original languageEnglish
Article number50
Pages (from-to)50
JournalCellular and molecular life sciences : CMLS
Issue number2
Publication statusPublished - 24 Jan 2023


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