Targeting circRNA-MAP4K2 for the treatment of diabetes-induced retinal vascular dysfunction

• Published in: Aging (Albany, NY.) Vol. 14; no. 15; pp. 6255 - 6268
• Main Authors: Ma, Cong, Shi, Ze-Hui, Han, Xiao-Yan, Liu, Chang, Yan, Biao, Du, Jian-Ling
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 11.08.2022
• Subjects: Cell Proliferation; Diabetes Mellitus - metabolism; Diabetic Retinopathy - genetics; Diabetic Retinopathy - metabolism; Endothelial Cells - metabolism; Germinal Center Kinases - metabolism; Glucose - metabolism; Humans; MicroRNAs - metabolism; Research Paper; RNA, Circular - genetics; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; retinal vascular complication; diabetic retinopathy; circular RNA; endothelial cell; angiogenic effect
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.204215

Diabetic retinopathy (DR) is an important ocular vascular disease in working-age adults. However, the molecular mechanism underlying retinal vascular dysfunction is still not fully understood in DR. Circular RNAs have been recognized as the crucial regulators in many biological processes and human diseases. Herein, we determined the role of circular RNA-MAP4K2 (cMAP4K2) in diabetes-induced retinal vascular dysfunction. The results showed that high glucose treatment led to increased levels of cMAP4K2 expression and . Silencing of cMAP4K2 could reduce endothelial cell viability, proliferation, migration, and tube formation and alleviate retinal vascular dysfunction as shown by decreased vascular leakage and inflammation. By contrast, cMAP4K2 overexpression had an opposite effect on retinal vascular dysfunction. Mechanistically, cMAP4K2 acted as miR-377 sponge to affect the biological activity of miR-377, which led to increased expression of vascular endothelial growth factor A (VEGFA). Clinically, cMAP4K2 expression was significantly up-regulated in the clinical sample of DR patients. Collectively, cMAP4K2 is shown as a potential target for the diagnosis and treatment of diabetic retinopathy.