Wenzhao Wang1, Dong He2, Jianan Chen3, Zhengdong Zhang1,4, Shaoyi Wang5, Yunpeng Jiang5, Jianlu Wei5. 1. Orthopedic Research Institute, Department of Orthopedics, West China Hospital，Sichuan University, Chengdu, Sichuan, China. 2. Department of Neurology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. 3. Department of Orthopedics, Cheeloo College of Medicine, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China. 4. Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China. 5. Department of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Abstract
OBJECTIVES: The spinal cord rarely repairs itself when damaged; however, methods for encouraging nerves to regrow are on the horizon. Although circular RNAs (circRNAs) contribute to various biological processes, including neuronal processes, their functions in the subacute phase of spinal cord injury (SCI) have not been elucidated. In this study, we identified a novel circRNA, named CircPlek, with increased expression in spinal tissues after SCI. MATERIALS AND METHODS: We predicted a regulatory relationship between CircPlek and miR-135b-5p, which showed the most obvious decrease in post-SCI expression. We established the CircPlek/miR-135b-5p/transforming growth factor-beta receptor type I (TGF-βR1) axis using a bioinformatics approach and further evaluated the potential function of the interaction network in vitro. RESULTS: We confirmed that in TGF-β1-induced fibroblasts, the overexpression of miR-135b-5p or/and inhibition of CircPlek inhibited fibrosis activation via the Smad pathway. Inhibitors of miR-135b-5p had antagonistic effects on CircPlek. CONCLUSIONS: the CircPlek/miR-135b-5p/TGF-βR1 axis may exert important functions in SCI and is a potential therapeutic target.
OBJECTIVES: The spinal cord rarely repairs itself when damaged; however, methods for encouraging nerves to regrow are on the horizon. Although circular RNAs (circRNAs) contribute to various biological processes, including neuronal processes, their functions in the subacute phase of spinal cord injury (SCI) have not been elucidated. In this study, we identified a novel circRNA, named CircPlek, with increased expression in spinal tissues after SCI. MATERIALS AND METHODS: We predicted a regulatory relationship between CircPlek and miR-135b-5p, which showed the most obvious decrease in post-SCI expression. We established the CircPlek/miR-135b-5p/transforming growth factor-beta receptor type I (TGF-βR1) axis using a bioinformatics approach and further evaluated the potential function of the interaction network in vitro. RESULTS: We confirmed that in TGF-β1-induced fibroblasts, the overexpression of miR-135b-5p or/and inhibition of CircPlek inhibited fibrosis activation via the Smad pathway. Inhibitors of miR-135b-5p had antagonistic effects on CircPlek. CONCLUSIONS: the CircPlek/miR-135b-5p/TGF-βR1 axis may exert important functions in SCI and is a potential therapeutic target.
Authors: Yu Yao; Xin Zhang; Jun Xu; Feng Gao; Yanni Wu; Xintao Cui; Li Wei; Jie Jiang; Xintao Wang Journal: Am J Transl Res Date: 2022-01-15 Impact factor: 4.060