CircARHGAP12 Triggers Mesenchymal Stromal Cell Autophagy to Facilitate its Effect on Repairing Diabetic Wounds by Sponging miR-301b-3p/ATG16L1 and miR-301b-3p/ULK2

Abstract

Circular RNAs have been confirmed to play vital roles in the development of human diseases. Nevertheless, their effects on modulating mesenchymal stromal cells (MSCs) to heal diabetic wounds are still elusive. In this study, our data revealed that MSCs treated with high glucose displayed an evident reduction in circARHGAP12 expression, whereas autophagy mediated by circARHGAP12 suppressed high glucose-triggered apoptosis of MSCs. Mechanistically, circARHGAP12 was capable of directly interacting with miR-301b-3p and subsequently sponged microRNA to modulate the expression of the miR-301b-3p target genes ATG16L1 and ULK2 and the downstream signaling pathway. Moreover, circARHGAP12 promoted the survival of MSCs in diabetic wounds in vivo and accelerated wound healing. Collectively, these results suggest that circARHGAP12/miR-301b-3p/ATG16L1 and circARHGAP12/miR-301b-3p/ULK2 regulatory networks might be an underlying therapeutic target for MSCs in diabetic wound healing.