2. Academic Validation
  3. CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis

CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis

  • Aging (Albany NY). 2021 May 11;13(9):12780-12799. doi: 10.18632/aging.202947.
Lei Yi 1 2 3,  Kai Ai 3,  Huiling Li 4,  Shuangfa Qiu 1 2,  Yijian Li 3,  Yinhuai Wang 3,  Xiaozhou Li 1 2,  Peilin Zheng 5 6,  Junxiang Chen 7,  Dengke Wu 1 2,  Xudong Xiang 1 2,  Xiangping Chai 1 2,  Yunchang Yuan 8,  Dongshan Zhang 1 2 7
Affiliations

Affiliations

  • 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 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.
  • 6 Department of Cellular Biology and Anatomy, Medical College of Georgia at Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
  • 7 Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
  • 8 Department of Chest Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
PMID: 33973871 DOI: 10.18632/aging.202947
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.

Keywords

HBEGF; KRAS; UUO; circRNA_30032; miR-96-5p.

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