COL4A2 activation of AKT signaling drives endothelial cell proliferation, migration, and angiogenesis in diabetic retinopathy.

In diabetes, diabetic retinopathy (DR) is the most prevalent consequence. Despite continuous advancements in treatment, current therapeutic approaches remain limited in efficacy and may carry side effects. A deeper understanding of DR pathogenesis is essential for generating more effective strategies. Bioinformatics tools were employed to analyze single-cell data from the GEO and SRA databases related to DR, aiming to identify target genes. STRING database was used to analyze PPI network of COL4A2. COL4A2 expression in retinal endothelial cells under high glucose conditions was detected using qRT-PCR and Western blot. Cells with COL4A2 knockdown or overexpression were constructed, and effects of COL4A2 expression levels on cell proliferation, migration, and angiogenesis were assessed through CCK-8 assays, Annexin V/PI staining, scratch assays, and tube formation assays. COL4A2-overexpressing cells were treated with an AKT inhibitor, and regulatory role of AKT signaling on proliferative properties of retinal vascular endothelial cells was validated by measuring cell viability, apoptosis, migration, and angiogenic capacity. High glucose conditions facilitated production of COL4A2 in human retinal capillary endothelial cells (HRCECs). COL4A2 level was correlated with proliferative properties of HRCECs, and overexpression of COL4A2 enhanced proliferation, migration, and angiogenesis of retinal endothelial cells. COL4A2 augmented proliferative-related characteristics of HRCECs by activating AKT signaling pathway. This study revealed critical role of COL4A2 in DR and elucidated its mechanism of regulating angiogenesis and cell proliferation through AKT signaling pathway. Our research gave us fresh perspectives on molecular causes of DR and a theoretical basis for creating COL4A2-targeting treatment plans.