Current Gene TherapyCurrent Gene TherapyCurrent Gene Therapy1566-52321875-5631Bentham Science64397810.2174/0115665232258527230919071328Life SciencesResearch ArticleExosome miR-30a-5p Regulates Glomerular Endothelial Cells' EndMT and Angiogenesis by Modulating Notch1/VEGF Signaling PathwayNingYaxianinfo@benthamscience.netZhouXiaochuninfo@benthamscience.netWangGouqininfo@benthamscience.netZhangLiliinfo@benthamscience.netWangJianqininfo@benthamscience.netDepartment of Nephrology, Second Hospital of Lanzhou UniversityDepartment of Nephrology, Second Hospital of Lanzhou University,0102202424215917707012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://transsyst.ru/1566-5232/article/view/643978

Background:Diabetic nephropathy (DN) is one of the microvascular complications of diabetes. Endothelial-mesenchymal transition (EndMT) and endothelial damage lead to abnormal angiogenesis in DN.

Objective:This study aimed to investigate the role of exosome miR-30a-5p in high glucose (HG)-induced glomerular endothelial cells (GECs) dysfunction and explore the underlying mechanisms.

Methods:GECs were cultured in normal glucose (5.5 mM) and HG (30 mM) conditions. The recipient GECs were transfected with exosome or miR-30a-5p mimic/inhibitor and then detected by using CCK-8 and flow cytometry assay. Luciferase analysis was used to verify miR-30a-5p acted on notch homolog protein 1 (Notch1). RT-qPCR and Western blot were used to detect the expression of VE-cadherin, α-SMA, vascular endothelial growth factor (VEGF) and Notch1. In vivo, exosome miR-30a-5p was administered to DN mice, and periodic acid-Schiff (PAS) staining, UTP levels, and HbA1c levels were measured.

Results:The expression of miR-30a-5p was downregulated in HG-treated GECs. Exosome miR-30a-5p significantly promoted cell proliferation, and migration and reduced apoptosis of GECs under HG conditions. MiR-30a-5p directly targeted the 3-UTR region of Notch1. Exosome miR-30a-5p reduced the expression levels of Notch1 and VEGF, both at mRNA and protein levels. Furthermore, exosome miR-30a-5p inhibited HG-induced EndMT, as evidenced by increased VE-cadherin and reduced α-SMA. In vivo studies demonstrated that exosome miR-30a-5p reduced serum HbA1c levels and 24-hour urine protein quantification.

Conclusion:This study provides evidence that exosome miR-30a-5p suppresses EndMT and abnormal angiogenesis of GECs by modulating the Notch1/VEGF signaling pathway. These findings suggest that exosome miR-30a-5p could be a potential therapeutic strategy for the treatment of DN.

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