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高糖刺激下体外Dll4/Notch-VEGF信号通路主要成分的初步研究

Preliminary Research of Main Components of Dll4/ Notch-VEGF Signaling Pathway Under High-Glucose Stimulation in vitro.

作者信息

Gao Na, Xiao Linghui, Tao Zheng, Zheng Yanlin, Wang Wanjie, Huang Hui

机构信息

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People's Republic of China.

Eye College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2022 Apr 18;15:1165-1171. doi: 10.2147/DMSO.S355004. eCollection 2022.

Abstract

PURPOSE

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.

摘要

目的

建立高糖(HG)应激细胞模型,研究高糖刺激下Dll4/Notch-VEGF信号通路主要成分的表达。

方法

首先建立HG条件培养细胞(人脐静脉内皮细胞,HUVECs)模型,然后通过RT-PCR和蛋白质印迹法分析有或无Notch通路阻断的HG应激细胞中Dll4、Notch1、Notch4和VEGF的表达。为观察细胞迁移,我们还评估了Transwell实验。

结果

选择用30mmol/L HG刺激的HUVECs作为细胞模型。RT-PCR和蛋白质印迹结果显示,HG刺激诱导Dll4、Notch1和VEGF的表达并下调Notch4。Notch通路阻断后表达逆转;同时,Notch通路阻断抑制HG条件下的细胞迁移。

结论

Notch4在对HG刺激的反应中的功能值得进一步研究。阻断Dll4/Notch和VEGF通路的联合治疗可能为我们提供一种抗血管生成的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d91/9031991/00e28577306b/DMSO-15-1165-g0001.jpg

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