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

• Published in: Pharmacological research 2024-06, Vol.204, p.107189-107189, Article 107189
• Main Authors: Wang, Wenzhao, Liu, Chang, He, Dong, Shi, Guidong, Song, Ping, Zhang, Boqing, Li, Tian, Wei, Jianlu, Jiang, Yunpeng, Ma, Liang
• Format: Article
• Language: English
• Subjects: Animals; CDR1as; CircRNA; Female; Fibrosis; Male; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-7; Nerve Regeneration; Receptor, Transforming Growth Factor-beta Type II - genetics; Receptor, Transforming Growth Factor-beta Type II - metabolism; Recovery of Function; RNA, Circular - genetics; RNA, Circular - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Smad Proteins - genetics; Smad Proteins - metabolism; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; Spinal cord injury
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2024.107189

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-βR2) 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-βR2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases. [Display omitted]