CircRNA CDR1as affects functional repair after spinal cord injury and regulates fibrosis through the SMAD pathway

作者全名:Wang, Wenzhao; Liu, Chang; He, Dong; Shi, Guidong; Song, Ping; Zhang, Boqing; Li, Tian; Wei, Jianlu; Jiang, Yunpeng; Ma, Liang

作者地址:[Wang, Wenzhao; Shi, Guidong; Wei, Jianlu; Jiang, Yunpeng] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Orthoped, Jinan 250012, Shandong, Peoples R China; [Ma, Liang] Shandong Univ Tradit Chinese Med, Dept Orthoped, Affiliated Hosp, Jinan, Shandong, Peoples R China; [Liu, Chang] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Chongqing, Peoples R China; [He, Dong] Shandong First Med Univ, Shandong Prov Hosp, Dept Neurosurg, Jinan, Shandong, Peoples R China; [He, Dong] Shandong Freda Biotech Co Ltd, Postdoctoral Sci Res Workstat, Jinan, Shandong, Peoples R China; [He, Dong] Shandong Univ, Cheeloo Coll Med, Dept Histol & Embryol, Sch Basic Med Sci, Jinan, Peoples R China; [Wang, Wenzhao; Song, Ping] Sichuan Univ, West China Hosp, Dept Orthoped, Chengdu, Sichuan, Peoples R China; [Song, Ping; Zhang, Boqing] Sichuan Univ, Natl Engn Res Ctr Biomat, Chengdu, Sichuan, Peoples R China; [Li, Tian] Fourth Mil Med Univ, Sch Basic Med, Xian 710032, Peoples R China

通信作者:Wei, JL; Jiang, YP (通讯作者),Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Orthoped, Jinan 250012, Shandong, Peoples R China.; Ma, L (通讯作者),Shandong Univ Tradit Chinese Med, Dept Orthoped, Affiliated Hosp, Jinan, Shandong, Peoples R China.

来源:PHARMACOLOGICAL RESEARCH

ESI学科分类:PHARMACOLOGY & TOXICOLOGY

WOS号:WOS:001222761600001

JCR分区:Q1

影响因子:9.1

年份:2024

卷号:204

期号: 

开始页: 

结束页: 

文献类型:Article

关键词:Spinal cord injury; Fibrosis; CircRNA; CDR1as; MiR-7

摘要:Spinal cord injury (SCI) is a complex problem in modern medicine. Fibroblast activation and fibroscarring after SCI impede nerve recovery. Non -coding RNA plays an important role in the progression of many diseases, but the study of its role in the progression of spinal fibrosis is still emerging. Here, we investigated the function of circular RNAs, specifically antisense to the cerebellar degeneration -related protein 1 (CDR1as), in spinal fibrosis and characterized its molecular mechanism and pathophysiology. The presence of CDR1as in the spinal cord was verified by sequencing and RNA expression assays. The effects of inhibition of CDR1as on scar formation, inflammation and nerve regeneration after spinal cord injury were investigated in vivo and in vitro. Further, gene expression of miR-7a-5p and protein expression of transforming Growth Factor Beta Receptor II (TGF-beta R2) were measured to evaluate their predicted interactions with CDR1as. The regulatory effects and activation pathways were subsequently verified by miR-7a-5p inhibitor and siCDR1as. These results indicate that CDR1as/miR-7a-5p/ TGF-beta R2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases.

基金机构:Key R & D Program of Shandong Prov- ince, China [2021CXGC010501]; Shandong Taishan Scholars Proj- ect [tsqn202211350]; Shandong Provincial Natural Science Foundation [ZR2021MH071, ZR2023QH223, ZR2023QH321]

基金资助正文:<BOLD>Acknowledgements</BOLD> The study was supported by Key R & D Program of Shandong Prov- ince, China (No. 2021CXGC010501) , Shandong Taishan Scholars Proj- ect (No. tsqn202211350) , Shandong Provincial Natural Science Foundation (No. ZR2021MH071, ZR2023QH223, and ZR2023QH321) .