Kruppel-Like Factor (KLF6) Regulates Oxidative Stress and Apoptosis of Human Retinal Pigment Epithelial Cells Induced by High Glucose Through Transcriptional Regulation of USP22 and the Downstream SIRT1/Nrf2 Pathway

被引:0
|
作者
Hu, Liping [1 ]
Zhang, Rui [1 ]
Wu, Jianhua [1 ]
Feng, Chao [1 ]
Jiang, Jingli [2 ]
机构
[1] Wuhan Univ, Aier Eye Hosp, Dept Fundus, Wuhan 430063, Hubei, Peoples R China
[2] Wenrong Hosp Hengdian, Dept Ophthalmol, Jinhua 322118, Zhejiang, Peoples R China
关键词
KLF6; USP22; Diabetic Retinopathy; High Glucose; Oxidative Stress and Apoptosis; SIRT1/Nrf2; Pathway; EXPRESSION; SYSTEM;
D O I
10.1166/jbt.2022.3104
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Oxidative stress and apoptosis play an important role in diabetic retinopathy (DR). KLF6 and its transcriptional regulator USP22 are abnormally expressed in DR, but the specific role and mechanism have not been reported. In this paper, we will discuss the specific roles and mechanisms of KLF6 and USP22 on oxidative stress and apoptosis in DR. In this study, RT-qPCR and western blot were used to detect the expression of KLF6 and USP22 in ARPE-19 cells. Subsequently, after KLF6 was overexpressed and USP22 expression was inhibited by cell transfection, the oxidative stress and apoptosis related indexes were detected by CCK-8, ELISA, TUNEL and other techniques to explore the mechanism. In addition, we used luciferase and ChIP to detect the association between KLF6 and USP22. Finally, the expression of proteins related to the SIRT1/Nrf2 pathway was detected by western blot. The results showed that silencing USP22 increased the activity, and inhibited apoptosis and oxidative stress of ARPE-19 cells induced by high glucose (HG). KLF6 transcriptionally activates USP22. Overexpression of KLF6 reversed the protective effects of silencing USP22 on HG-induced ARPE-19 cells against apoptosis and antioxidant stress, which may be achieved by regulating the SIRT1/Nrf2 pathway. In conclusion, KLF6 regulated oxidative stress and apoptosis of ARPE-19 cells induced by high glucose through transcriptional regulation of USP22 and the downstream SIRT1/Nrf2 pathway.
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页码:1853 / 1862
页数:10
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