MiR ‐155‐5p promotes endothelial–mesenchymal transition and oxidative stress in diabetic retinopathy

Aims MicroRNA (miRNA) has been confirmed to be related to gene expression regulation and disease progression. However, the role of miR‐155‐5p in diabetic retinopathy remains unclear. Materials and Methods The retinal microvascular endothelial cells (RMECs) were treated with high glucose, and then the changes of miR‐155‐5p, endothelial cell markers (CD31 and VE‐cadherin), mesenchymal cell markers (SM22α and α‐SMA), and VEGF were detected by RT‐qPCR. The apoptotic markers (Bax, Bcl‐2, cleaved caspase‐3) were detected by Western blotting. Additionally, miRNA inhibitors or small interfering RNA were used to regulate the levels of miR‐155‐5p and DDAH1. Subsequently, the changes in endothelial–mesenchymal transition markers, oxidative stress markers, and apoptotic proteins were observed. The regulatory relationship between miR‐155‐5p and DDAH1 was investigated using dual‐luciferase reporter assays, RNA immunoprecipitation, and RNA pull‐down assays. Results After culturing RMECs with high glucose, the level of miR‐155‐5p increased. After the miR‐155‐5p level was reduced, the levels of CD31 and VE‐cadherin increased, while the levels of SM22α, α‐SMA and VEGF decreased. Additionally, the downregulation of miR‐155‐5p significantly inhibited the increase in ROS and Malondialdehyde (MDA) levels as well as cell apoptosis. DDAH1 is the downstream target of miR‐155‐5p. The downregulation of DDAH1 significantly weakened the inhibitory effects of miR‐155‐5p downregulation on endothelial–mesenchymal transition, oxidative stress, and cell apoptosis. Conclusions In diabetic retinopathy, miR‐155‐5p affects the endothelial–mesenchymal transition process and oxidative stress levels of RMECs through DDAH1 and reduces cell apoptosis induced by high glucose.