Circular RNA COL1A2 promotes angiogenesis via regulating miR-29b/VEGF axis in diabetic retinopathy

Abstract

AimsThe dysregulation of circular RNAs (circRNAs) has been implicated in the progression of diabetic retinopathy (DR). This study aims to explore the role and underlying mechanism of hsa_circ_0081108 (circCOL1A2) in DR. Materials and methodscircCOL1A2, vascular endothelial growth factor (VEGF) and miR-29b expression levels in human retinal microvascular endothelial cells (hRMECs) were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting. The biological functions of hRMECs were evaluated by MTT, transwell, tube formation, and vascular permeability assays, respectively. The interaction between miR-29b and circCOL1A2/VEGF was determined by dual luciferase assay. The release of VEGF was examined by ELISA. The in vivo role of circCOL1A2 was further verified in streptozotocin (STZ)-induced DR in mice. The pathological changes and VEGF expression in retinal tissues were detected by hematoxylin and eosin (HE) and immunohistochemical staining. Key findingsHigh glucose (HG) challenge led to increased circCOL1A2, VEGF, MMP-2, MMP-9 levels, but decreased miR-29b level in hRMECs. In addition, circCOL1A2 sponged miR-29b to promote VEGF expression. Silencing of circCOL1A2 inhibited HG-induced proliferation, migration, angiogenesis and vascular permeability of hRMECs via enhancing miR-29b expression. Moreover, circCOL1A2/miR-29b axis participated in HG-induced increase in angiogenesis-related protein expression. Finally, circCOL1A2 knockdown suppressed angiogenesis via regulating miR-29b/VEGF axis in DR mice. SignificancecircCOL1A2 facilities angiogenesis during the pathological progression of DR via regulating miR-29b/VEGF axis, suggesting that targeting circCOL1A2 may be a potential treatment for DR.