Diabetes, Metabolic Syndrome and Obesity (Apr 2022)
Preliminary Research of Main Components of Dll4/ Notch-VEGF Signaling Pathway Under High-Glucose Stimulation in vitro
Abstract
Na Gao,1,* Linghui Xiao,1,* Zheng Tao,2 Yanlin Zheng,1 Wanjie Wang,1 Hui Huang1 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Eye College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Huang, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Jinniu District, Chengdu, 610072, Sichuan Province, People’s Republic of China, Tel +86-18782917219, Fax +86-28-87732407, Email [email protected]: To establish a high-glucose (HG) stressed cell model and study the expression of main components of the Dll4/Notch-VEGF signaling pathway under high-glucose stimulation.Methods: A model of HG-conditioned cells (human umbilical vein endothelial cells, HUVECs) was first established, and then the expression of Dll4, Notch1, Notch4 and VEGF in HG-stressed cells with or without Notch pathway blockage was analyzed by RT-PCR and Western blot. To observe cell migration, we also evaluated the Transwell assay.Results: HUVECs stimulated with 30mmol/L HG was selected as a cell model. RT-PCR and Western blot results showed that HG stimulation induced the expression of Dll4, Notch1 and VEGF and downregulated Notch4. The expressions were reversed after Notch pathway blockage; meanwhile, the blockage of Notch pathway inhibited cell migration under HG condition.Conclusion: The function of Notch4 in responses to HG stimulation deserves further researching. Combination therapy by blocking Dll4/Notch and VEGF pathways may provide us with a new way for anti-neovascularization.Keywords: Dll4, Notch1, Notch4, VEGF, endothelial cells
