TY - JOUR
T1 - Circ-sh3rf3/GATA-4/miR-29a regulatory axis in fibroblast-myofibroblast differentiation and myocardial fibrosis
AU - Ma, Cai-Xia
AU - Wei, Zhi-Ru
AU - Sun, Tong
AU - Yang, Ming-Hui
AU - Sun, Yu-Qie
AU - Kai, Kun-Lun
AU - Shi, Jia-Chen
AU - Zhou, Meng-Jiao
AU - Wang, Zi-Wei
AU - Chen, Jing
AU - Li, Wei
AU - Wang, Tian-Qi
AU - Zhang, Shan-Feng
AU - Xue, Lixiang
AU - Zhang, Min
AU - Yin, Qianqian
AU - Zang, Ming-Xi
N1 - Funding Information:
This study was supported by the National Natural Science Foundation of China (Nos. 82072975, 81771631, and 32171179), the High-Level Talents of Henan Province, particularly the support for the Central Plains Thousand Talents Program, which are the leading talents of Central Plains Basic Research (ZYQR201810120); the key project of discipline construction of Zhengzhou University in 2020 (XKZDQY202002), 2022 Henan Province Science and Technology R&D Program Joint Fund (Cultivation of Superior Disciplines, 222301420094), and Henan Province Science and Technology Projects (202102310057).
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
PY - 2023/1/24
Y1 - 2023/1/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85146881500&partnerID=8YFLogxK
U2 - 10.1007/s00018-023-04699-7
DO - 10.1007/s00018-023-04699-7
M3 - Article
C2 - 36694058
SN - 1420-682X
VL - 80
SP - 50
JO - Cellular and molecular life sciences : CMLS
JF - Cellular and molecular life sciences : CMLS
IS - 2
M1 - 50
ER -