Role of the Receptor for Advanced Glycation End Products in Heat Stress-Induced Endothelial Hyperpermeability in Acute Lung Injury.
Role of the Receptor for Advanced Glycation End Products in Heat Stress-Induced Endothelial Hyperpermeability in Acute Lung Injury.
复制标题
高级糖基化终产物受体在急性肺损伤热应激诱导的内皮通透性过高中的作用
DOI：
10.3389/fphys.2020.01087
复制
发表时间：
2020
影响因子：
4
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Zhou G;Chen Z;Li J;Guo X;Qin K;Luo J;Hu J;Huang Q;Su L;Guo X;Xu Q
目的 研究晚期糖基化终末产物受体（RAGE）在热应激所致内皮屏障功能障碍中的作用，进一步探讨RAGE参与热诱发内皮反应的信号通路，为临床治疗中暑所致急性肺损伤（ALI）寻找新靶点。方法本研究采用RAGE基因敲除小鼠建立中暑动物模型。我们通过评估BALF（支气管肺泡灌洗液）中白细胞、中性粒细胞和蛋白浓度、肺湿/干比、组织病理学变化、肺组织形态超微结构和动脉血气分析，观察RAGE在小鼠中暑所致急性肺损伤中的作用。为了进一步研究其机制，我们建立了HUVEC热应激模型，重点研究了RAGE及其信号通路在热应激引起的内皮屏障功能障碍中的作用，测量了跨内皮电阻（TEER）和蛋白质印迹。结果RAGE在中暑小鼠急性肺损伤中起关键作用。机制C-Jun位于RAGE基因的启动子区域。 C-Jun 增加 RAGE 蛋白表达，而 HSF1 抑制 RAGE 蛋白表达。然后，过表达的 RAGE 蛋白通过在热应激下激活 ERK 和 P38 MAPK 来增加 HUVEC 单层通透性。结论本研究表明RAGE在急性肺损伤中热应激诱导的内皮通透性过高中的关键作用，并表明RAGE可能成为保护患者免受中暑引起的急性肺损伤的潜在治疗靶点。
Objective To study the role of the receptor for advanced glycation end products (RAGE) in endothelial barrier dysfunction induced by heat stress, to further explore the signal pathway by which RAGE contributes to heat-induced endothelia response, and thereby find a novel target for the clinical treatment of ALI (acute lung injury) induced by heatstroke. Methods This study established the animal model of heatstroke using RAGE knockout mice. We observed the role of RAGE in acute lung injury induced by heatstroke in mice by evaluating the leukocytes, neutrophils, and protein concentration in BALF (Bronchoalveolar lavage fluids), lung wet/dry ratio, histopathological changes, and the morphological ultrastructure of lung tissue and arterial blood gas analysis. To further study the mechanism, we established a heat stress model of HUVEC and concentrated on the role of RAGE and its signal pathway in the endothelial barrier dysfunction induced by heat stress, measuring Transendothelial electrical resistance (TEER) and western blot. Results RAGE played a key role in acute lung injury induced by heatstroke in mice. The mechanism C-Jun is located in the promoter region of the RAGE gene. C-Jun increased the RAGE protein expression while HSF1 suppressed RAGE protein expression. The overexpressed RAGE protein then increased HUVEC monolayer permeability by activating ERK and P38 MAPK under heat stress. Conclusion This study indicates the critical role of RAGE in heat stress-induced endothelial hyperpermeability in acute lung injury and suggests that RAGE could be a potential therapeutic target in protecting patients against acute lung injury induced by heatstroke.
登录
查看更多内容
影响因子：
--
作者：
Yang HH;Chang CP;Cheng RT;Lin MT
通讯作者：
Lin MT
影响因子：
5.3
作者：
Wang, XZ;Grammatikakis, N;Calderwood, SK
通讯作者：
Calderwood, SK
Src 在 AGE 诱导的内皮细胞增殖、迁移和肾小管形成中发挥重要作用
影响因子：
4
作者：
Li P;Chen D;Cui Y;Zhang W;Weng J;Yu L;Chen L;Chen Z;Su H;Yu S;Wu J;Huang Q;Guo X
通讯作者：
Guo X
DOI：
10.1186/cc6164
发表时间：
2008
期刊：
Critical care (London, England)
影响因子：
--
作者：
Bopp C;Bierhaus A;Hofer S;Bouchon A;Nawroth PP;Martin E;Weigand MA
通讯作者：
Weigand MA
影响因子：
3.7
作者：
Lee CC;Wang CN;Lee YL;Tsai YR;Liu JJ
通讯作者：
Liu JJ