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Overexpression of calcitonin gene-related peptide protects mouse cerebral microvascular endothelial cells from high-glucose-induced damage via ERK/HIF-1/VEGF signaling.
The Journal of Physiological Sciences ( IF 2.6 ) Pub Date : 2019-09-05 , DOI: 10.1007/s12576-019-00708-2
Yanjun Guo 1, 2 , Qin Zhang 1, 2 , Huilu Chen 1, 2 , Yixuan Jiang 1, 2 , Ping Gong 1, 2
Affiliation  

In the diabetic brain, hyperglycemia damages the cerebrovasculature and impairs neurovascular crosstalk. Calcitonin gene-related peptide (CGRP) is an important neuropeptide that is active in the vascular system. In this study, we aimed to investigate whether CGRP is involved in the high-glucose-induced damage in mouse cerebral microvascular endothelial (b.END3) cells and the possible mechanism in vitro. The overexpression of CGRP by lentiviral transduction inhibited cell apoptosis but not proliferation. In contrast to the promoting of angiogenesis and migration under normal glucose, CGRP inhibited hyperglycemia-induced tube formation but had no effect on migration. Calcitonin gene-related peptide partly reduced the increased level of intracellular reactive oxygen species (ROS) and altered nitric oxide synthase mRNA expression. Furthermore, CGRP suppressed the increased HIF-1α/VEGF-A expression and the phosphorylation of ERK1/2 in hyperglycemia. The ERK inhibitor U0126 showed similar inhibition of cell apoptosis, tube formation and HIF-1α/VEGF expression as that exhibited by lenti-CGRP. These findings demonstrate the protective role of CGRP overexpression against high-glucose-induced cerebrovascular changes in b.END3 cells, possibly through the inhibition of ERK/HIF-1/VEGF signaling.

中文翻译:


降钙素基因相关肽的过表达通过 ERK/HIF-1/VEGF 信号传导保护小鼠脑微血管内皮细胞免受高糖诱导的损伤。



在糖尿病患者的大脑中,高血糖会损害脑血管系统并损害神经血管串扰。降钙素基因相关肽(CGRP)是一种在血管系统中活跃的重要神经肽。在本研究中,我们旨在体外研究CGRP是否参与高糖诱导的小鼠脑微血管内皮(b.END3)细胞损伤及其可能的机制。慢病毒转导过度表达 CGRP 抑制细胞凋亡,但不抑制增殖。与正常血糖下促进血管生成和迁移相反,CGRP 抑制高血糖诱导的血管形成,但对迁移没有影响。降钙素基因相关肽部分降低了细胞内活性氧 (ROS) 水平的升高并改变了一氧化氮合酶 mRNA 的表达。此外,CGRP 抑制高血糖时 HIF-1α/VEGF-A 表达的增加和 ERK1/2 的磷酸化。 ERK 抑制剂 U0126 对细胞凋亡、管形成和 HIF-1α/VEGF 表达的抑制作用与 lenti-CGRP 相似。这些发现证明了 CGRP 过表达对 b.END3 细胞中高葡萄糖诱导的脑血管变化的保护作用,可能是通过抑制 ERK/HIF-1/VEGF 信号传导来实现的。
更新日期:2019-11-01
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