Title:Exosome miR-30a-5p Regulates Glomerular Endothelial Cells' EndMT
and Angiogenesis by Modulating Notch1/VEGF Signaling Pathway
Volume: 24
Issue: 2
关键词:
糖尿病肾病，外泌体，miR-30a-5p, Notch1，血管生成，肾小球内皮细胞。
摘要:
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.
Objectives: 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.
