The circ_006573/miR-376b-3p Axis Advances Spinal Cord Functional Recovery after Injury by Modulating Vascular Regeneration.

Abnormal expression of non-coding RNAs after spinal cord injury (SCI) is associated with pathophysiological outcomes. We bioinformatically predicted a circRNA-miRNA-mRNA axis in SCI. A total of 4690 mRNAs, 17 miRNAs, and 3928 circRNAs were differentially expressed, with co-expressed RNAs predicted to regulate pathways related to wound healing. Among the most highly differentially expressed circRNAs, circ_006573, but not circ_016395, weakened the viability and migration of rat aortic endothelial cells, and its biological effects were rescued with miR-376b-3p mimics. Furthermore, circ_006573 overexpression induced changes in Cebpb, IL-18, and Plscr1 expression that were reversed by miR-376b-3p. In a rat model, circ_006573 shRNA administration improved the pathological manifestations of SCI and ameliorated motor function. Moreover, the expression of CD31, CD34, and VEGF-A in spinal cord tissues was significantly elevated after circ_006573 shRNA treatment, indicating that circ_006573 may be involved in vascular regeneration and functional recovery after SCI. Thus, the circ_006573-miR-376b-3p axis offers a foundation for understanding pathophysiological mechanisms and predicting strategies for treating SCI.