Research Paper Volume 13, Issue 9 pp 12780—12799
CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis
- 1 Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 2 Emergency Medicine and Difficult Diseases Institute, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 3 Department of Urology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 4 Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 5 Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 6 Department of Chest Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
- 7 Department of Endocrinology, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China
- 8 Department of Cellular Biology and Anatomy, Medical College of Georgia at Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, GA 30904, USA
Received: October 5, 2020 Accepted: December 23, 2020 Published: May 11, 2021
https://doi.org/10.18632/aging.202947How to Cite
Abstract
In this study, we investigated the role of circular RNA_30032 (circRNA_30032) in renal fibrosis and the underlying mechanisms. The study was carried out using TGF-β1-induced BUMPT cells and unilateral ureteral obstruction (UUO)-induced mice, respectively, as in vitro and in vivo models. CircRNA_30032 expression was significantly increased by 9.15- and 16.6-fold on days 3 and 7, respectively, in the renal tissues of UUO model mice. In TGF-β1-treated BUMPT cells, circRNA_30032 expression was induced by activation of the p38 mitogen-activated protein kinase signaling pathway. Quantitative real-time PCR, western blotting and dual luciferase reporter assays showed that circRNA_30032 mediated TGF-β1-induced and UUO-induced renal fibrosis by sponging miR-96-5p and increasing the expression of profibrotic proteins, including HBEGF, KRAS, collagen I, collagen III and fibronectin. CircRNA_30032 silencing significantly reduced renal fibrosis in UUO model mice by increasing miR-96-5p levels and decreasing levels of HBEGF and KRAS. These results demonstrate that circRNA_30032 promotes renal fibrosis via the miR-96-5p/HBEGF/KRAS axis and suggest that circRNA_30032 is a potential therapeutic target for treatment of renal fibrosis.