LIN28A attenuates high glucose-induced retinal pigmented epithelium injury through activating SIRT1-dependent autophagy  

作　　者：Dan-Qing Yu Song-Ping Yu Jing Wu Li-Na Lan Bang-Xun Mao 

机构地区：[1]Department of Endocrinology,Affiliated Lishui Hospital of Zhejiang University,Lishui 323000,Zhejiang Province,China [2]Department of Ophthalmology,Affiliated Lishui Hospital of Zhejiang University,Lishui 323000,Zhejiang Province,China

出　　处：《International Journal of Ophthalmology(English edition)》2023年第9期1465-1474,共10页国际眼科杂志（英文版）

基　　金：Supported by Medical and Health Science and Technology Project of Zhejiang Province(No.2023KY1356).

摘　　要：AIM:To evaluate the effects of LIN28A(human)on high glucose-induced retinal pigmented epithelium(RPE)cell injury and its possible mechanism.METHODS:Diabetic retinopathy model was generated following 48h of exposure to 30 mmol/L high glucose(HG)in ARPE-19 cells.Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot tested the expression of the corresponding genes and proteins.Cell viability as well as apoptosis was determined through cell counting kit-8(CCK-8)and flow cytometry assays.Immunofluorescence assay was adopted to evaluate autophagy activity.Caspase 3 activity,oxidative stress markers,and cytokines were appraised adopting their commercial kits,respectively.Finally,ARPE-19 cells were preincubated with EX527,a Sirtuin 1(SIRT1)inhibitor,prior to HG stimulation to validate the regulatory mechanism.RESULTS:LIN28A was downregulated in HG-challenged ARPE-19 cells.LIN28A overexpression greatly inhibited HGinduced ARPE-19 cell viability loss,apoptosis,oxidative damage as well as inflammatory response.Meanwhile,the repressed autophagy and SIRT1 in ARPE-19 cells challenged with HG were elevated after LIN28A overexpression.In addition,treatment of EX527 greatly inhibited the activated autophagy following LIN28A overexpression and partly abolished the protective role of LIN28A against HG-elicited apoptosis,oxidative damage as well as inflammation in ARPE-19 cells.CONCLUSION:LIN28A exerts a protective role against HG-elicited RPE oxidative damage,inflammation,as well as apoptosis via regulating SIRT1/autophagy.

关 键 词：LIN28A retinal pigmented epithelial cells high glucose Sirtuin 1 AUTOPHAGY oxidative stress 

分 类 号：R774.1[医药卫生—眼科] R587.2[医药卫生—临床医学]