GLP-1 Treatment Improves Diabetic Retinopathy by Alleviating Autophagy through GLP-1R-ERK1/2-HDAC6 Signaling Pathway.
GLP-1 Treatment Improves Diabetic Retinopathy by Alleviating Autophagy through GLP-1R-ERK1/2-HDAC6 Signaling Pathway.
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DOI：
10.7150/ijms.20962
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发表时间：
2017
影响因子：
3.6
通讯作者：
Hui H
中科院分区：
文献类型：
--
作者：
Cai X;Li J;Wang M;She M;Tang Y;Li J;Li H;Hui H
目的：氧化应激可诱导视网膜细胞的凋亡和自噬，与糖尿病视网膜病变(DR)的发病密切相关。氧化应激诱导的自噬被认为是过度刺激的自噬，加速了DR的进展。本研究旨在观察GLP-1对2型糖尿病大鼠视网膜细胞凋亡和自噬的保护作用，并揭示其可能的机制。方法：用高糖高脂饲料喂养并注射链脲佐菌素建立2型糖尿病大鼠模型。糖尿病大鼠发病后应用GLP-1治疗1周。用Western blotting或免疫组织化学方法检测氧化应激相关酶、视网膜GLP-1R、线粒体依赖的凋亡相关基因、自噬标志物和自噬相关途径基因的表达。结果：GLP-1治疗可降低DR中NOX3和SOD2的表达，增加BCL2的表达，降低Caspase3和LC3B的表达，恢复DR中GLP-1R的表达，降低磷酸化的AKT和ERK1/2的水平，同时降低HDAC6的水平。结论：GLP-1治疗可以减轻氧化应激诱导的自噬，这种保护作用可能是通过GLP-1R-ERK1/2-HDAC6信号转导途径实现的。
Objective: Apoptosis and autophagy of retinal cells, which may be induced by oxidative stress, are tightly associated with the pathogenesis of diabetic retinopathy (DR). The autophagy induced by oxidative stress is considered as excessively stimulated autophagy, which accelerates the progression of DR. This study aims to investigate the protective effect of GLP-1 treatment on alleviating apoptosis and autophagy of retinal cells in type 2 diabetic rats and reveals its possible mechanism. Methods: Type 2 diabetic rats were induced by fed with high sugar, high fat diet and followed with streptozotocin injection. GLP-1 was applied to treat the diabetic rats for one week after the onset of diabetes. The expressions of oxidative stress-related enzymes, retinal GLP-1R, mitochondria-dependent apoptosis- related genes, autophagy markers, and autophagy-associated pathway genes were studied by Western blotting or immunohistochemistry analysis. Results: GLP-1treatment reduced the levels of NOX3 and SOD2 in DR. The expression of BCL2 was increased, while the levels of caspase3 and LC3B were reduced through GLP-1 treatment in DR. GLP-1 treatment restored the GLP-1R expression and decreased the levels of phosphorylated AKT and phosphorylated ERK1/2, which was accompanied with the reduction of the HDAC6 levels in DR. Conclusions: GLP-1 treatment can alleviate autophagy which may be induced by oxidative stress; this protective effect is likely through GLP-1R-ERK1/2-HDAC6 signaling pathway.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
影响因子：
3.4
作者：
Fan, Yichao;Liu, Kun;Zhang, Yu
通讯作者：
Zhang, Yu
影响因子：
3.4
作者：
Sundling, Vibeke;Platou, Carl G. P.;Gulbrandsen, Pal
通讯作者：
Gulbrandsen, Pal
影响因子：
4.3
作者：
Jin J;Min H;Kim SJ;Oh S;Kim K;Yu HG;Park T;Kim Y
通讯作者：
Kim Y
影响因子：
4
作者：
Chen, Yongqiang;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.