眼科新进展2025,Vol.45Issue(8):603-608,6.DOI:10.13389/j.cnki.rao.2025.0104
miR-155-5p在糖尿病视网膜病变中的作用机制和意义
The mechanism of action and significance of miR-155-5p in diabetic retinopathy
摘要
Abstract
Objective To elucidate the role of miR-155-5p in diabetic retinopathy(DR)and its potential mechanism.Methods Twelve peripheral blood samples were collected from the Ophthalmology Department of the First Affiliated Hospital of Jinzhou Medical University.Among them,six blood samples from healthy individuals were set as the control group,and the other six blood samples from DR patients were set as the DR group.Reverse transcription-polymerase chain reaction(RT-PCR)was used to verify the expression levels of miR-155-5p in two groups of blood samples.The effects of miR-155-5p on cell proliferation,apoptosis,autophagy,and inflammation related proteins[including P62,LC3B,NOD-like receptor protein 3(NLRP3),IL-1β,and pro-caspase-1]were observed using a high glucose(100 mmol·L-1)-induced DR cell model.Some ARPE-19 cells were intervened with the miR-155-5p inhibitor or its negative control inhibitor(i.e.,NC-inhibitor),and then they were divided into the HG+miR-155-5p-inhibitor group and the HG+NC-inhibitor group.Cells cul-tured in a glucose-free medium were set as the Control group.Some ARPE-19 cells were treated with miR-155-5p-mimics or their negative control inhibitors(i.e.,NC-mimics),and then they were classified into the HG+miR-155-5p-mimics group and the HG+NC-mimics group.Dual luciferase reporter gene analysis revealed the interaction between miR-155-5p and si-lent information regulator 1(SIRT1).Cells in the HG+miR-155-5 p-mimics and HG+NC-mimics groups were co-transfected with SIRT1-3'UTR-WT and SIRT1-3'UTR-MUT,respectively.The expression levels of luciferase in both groups of cells were detected.The recovery experiment verified that miR-155-5p affected autophagy and inflammatory responses in DR model cells by regulating SIRT1 expression.Cells co-transfected with miR-155-5p-mimics and pcDNA3.1-SIRT1 overexpres-sion plasmids were included in the HG+miR-155-5p-mimics+SIRT1 group.Cells transfected only with miR-155-5p-mimics or their negative control inhibitors were included in the HG+miR-155-5p-mimics group and the HG+NC-mimics group,re-spectively.Cell proliferation,apoptosis,and the expression levels of apoptosis and autophagy related proteins were detec-ted in each group.Results The expression level of miR-155-5p in the DR group was higher than that in the control group(t=-8.078,P<0.001).Compared with the HG+NC-inhibitor group,the HG+miR-155-5p-inhibitor group showed en-hanced cell proliferation ability,decreased miR-155-5p level,and weakened apoptosis(all P<0.001).Compared with the HG+NC-mimics group,the HG+miR-155-5p-mimics group showed decreased cell proliferation ability,increased miR-155-5p levels,enhanced apoptosis,lowered levels of the autophagy protein P62,and elevated levels of the autophagy protein LC3B and inflammatory proteins NLRP3,IL-1 β,and pro-caspase-1(all P<0.01).Compared with those in the HG+NC-mimics group,the expression levels of SIRT1 mRNAs and proteins in the HG+miR-155-5p-mimics group decreased(both P<0.001).The luciferase activity in the HG+miR-155-5p-mimics group decreased after the transfection with SIRT1-3'UTR-WT(P<0.001).Compared with the HG+miR-155-5p-mimics group,the HG+miR-155-5p-mimics+SIRT1 group showed enhanced cell proliferation,decreased miR-155-5p levels,weakened apoptosis,elevated levels of SIRT1 and P62 proteins,and reduced levels of LC3B and inflammatory proteins NLRP3,IL-1 β,and pro-caspase-1(all P<0.05).SIRT1 was identified as a downstream target of miR-155-5p.Conclusion MiR-155-5p inhibits the proliferation of DR model cells by targeting SIRT1,thus promoting the apoptosis,autophagy,and inflammatory response of retinal epithelial cells.关键词
糖尿病视网膜病变/miR-155-5-p/SIRT1/自噬/炎症Key words
diabetic retinopathy/miR-155-5-p/silent information regulator 1/autophagy/inflammation分类
医药卫生引用本文复制引用
娄瑞特,李兵..miR-155-5p在糖尿病视网膜病变中的作用机制和意义[J].眼科新进展,2025,45(8):603-608,6.基金项目
辽宁省自然科学基金(编号:2013022001) (编号:2013022001)