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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

Lei Yi1,2,3, Kai Ai3, Huiling Li4, Shuangfa Qiu1,2, Yijian Li3, Yinhuai Wang3, Xiaozhou Li1,2, Peilin Zheng7,8, Junxiang Chen5, Dengke Wu1,2, Xudong Xiang1,2, Xiangping Chai1,2, Yunchang Yuan6, Dongshan Zhang1,2,5
  • 1Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
  • 2Emergency Medicine and Difficult Diseases Institute, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
  • 3Department of Urology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
  • 4Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
  • 5Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
  • 6Department of Chest Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
  • 7Department 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
  • 8Department of Cellular Biology and Anatomy, Medical College of Georgia at Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, GA 30904, USA
* Co-first author
Received: October 5, 2020Accepted: December 23, 2020Published: May 11, 2021

Copyright: © 2021 Yi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.