GLP-1 RA Improves Diabetic Retinopathy by Protecting the Blood-Retinal Barrier through GLP-1R-ROCK-p-MLC Signaling Pathway.
GLP-1 RA Improves Diabetic Retinopathy by Protecting the Blood-Retinal Barrier through GLP-1R-ROCK-p-MLC Signaling Pathway.
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GLP-1 RA 通过 GLP-1R-ROCK-p-MLC 信号通路保护血视网膜屏障来改善糖尿病视网膜病变
DOI：
10.1155/2022/1861940
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发表时间：
2022
影响因子：
4.3
通讯作者：
Luo, Zuojie
中科院分区：
文献类型：
--
作者：
Wei, Liufeng;Mo, Weiwei;Lan, Shanshan;Yang, Haiyan;Huang, Zhenxing;Liang, Xinghuan;Li, Li;Xian, Jing;Xie, Xuemei;Qin, Yingfen;Lin, Faquan;Luo, Zuojie
背景GLP-1受体激动剂(GLP-1RA)是临床上常见的预防糖尿病并发症的药物，如糖尿病视网膜病变(DR)。已有研究表明，RhoA/ROCK通路在DR的发生发展中起重要作用，但GLP-1RA与DR的具体作用机制尚不清楚。本研究的目的是探讨GLP-1RA对DR的保护作用的主要机制。通过HE染色和透射电子显微镜观察视网膜结构的变化。免疫印迹或免疫荧光分析检测视网膜GLP-1R、血-视网膜屏障(BRB)相关蛋白、炎症因子及相关通路蛋白的表达。结果GLP-1RA治疗可降低糖尿病小鼠的血糖、血脂水平和体重，改善视网膜厚度、形态和血管超微结构。此外，恢复GLP-1R的表达，增加occludin和ZO-1的水平，减少白蛋白的表达，可以减少视网膜渗漏，并通过抑制RhoA/ROCK通路来改善BRB。结论GLP-1RA对视网膜的保护作用可能是通过GLP-1R-ROCK-p-MLC信号通路实现的。
Background GLP-1 receptor agonists (GLP-1RA) are common clinical agents that are clinically protective against diabetic complications, such as diabetic retinopathy (DR). Previous studies have shown that the RhoA/ROCK pathway plays an important role in the development of DR. However, the specific mechanism of action between GLP-1RA and DR remains unclear. The aim of this study was thus to investigate the main mechanism involved in the protective effect of GLP-1RA on DR. Methods Type 2 diabetic mice were fed a high-sugar, high-fat diet. Changes in the retinal structure were observed via HE staining and transmission electron microscopy. The expression of retinal GLP-1R, blood-retinal barrier- (BRB-) related proteins, inflammatory factors, and related pathway proteins were studied via Western blot or immunohistochemistry/immunofluorescence analysis. Results GLP-1RA treatment reduced the blood glucose and lipid levels as well as the body weight of the diabetic mice while also improving retinal thickness, morphology, and vascular ultrastructure. Moreover, restored GLP-1R expression, increased Occludin and ZO-1 levels, and decreased albumin expression led to reduced retinal leakage and improved the BRB by inhibiting the RhoA/ROCK pathway. Conclusions We found that the protective effect of GLP-1RA on the retina may be realized through the GLP-1R-ROCK-p-MLC signaling pathway.
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影响因子：
1.8
作者：
Díaz-Coránguez M;Ramos C;Antonetti DA
通讯作者：
Antonetti DA
影响因子：
40.5
作者：
Antonetti, David A.;Silva, Paolo S.;Stitt, Alan W.
通讯作者：
Stitt, Alan W.
影响因子：
3.8
作者：
Li, Yi Ming;Zhang, Li Hui;Tong, Nan Wei
通讯作者：
Tong, Nan Wei
影响因子：
3.9
作者：
Sampedro, Joel;Bogdanov, Patricia;Hernandez, Cristina
通讯作者：
Hernandez, Cristina
DOI：
10.1111/dom.14465
发表时间：
2021-10
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Bonora E;Frias JP;Tinahones FJ;Van J;Malik RE;Yu Z;Mody R;Bethel A;Kwan AYM;Cox DA
通讯作者：
Cox DA