临床眼科杂志2025，Vol.33Issue(5)：454-459,6.DOI:10.3969/j.issn.1006-8422.2025.05.013
HIF-1α/ANGPTL4表达变化对ARPE-19细胞迁移和单层细胞通透性的影响及其可能的机制研究
The effect of HIF-1α/ANGPTL4 expression changes on ARPE-19 cell migration and monolayer cell perme-ability and its possible mechanism
摘要
Abstract
Objective To analyze the effect of changes in the expression of hypoxia-inducible factor-1α/angiogenin-like protein 4(HIF-1α/ANGPTL4)on human retinal pigment epithelial cell(ARPE-19)migration and mono-layer cell permeability,and their possible pathological mechanism.Methods Prospective case-control study.30 clean-grade,healthy male Wistar rats were randomly selected to establish a diabetic rat model.The rats were randomly divided into the control group(n=15)and diabetic group(n=15).The control group and diabetic group were both randomly di-vided into 4 w(n=5),8 w(n=5)and 12 w groups(n=5).Rat retinal tissue samples were taken,and changes in both reti-nal structure and retinal expression levels of HIF-1α and ANGPTL4 for each group were measured.ARPE-19 were taken and cultured.The cells were divided into normal,hypoxia 8 hour,hypoxia 16 hour,and hypoxia 24 hour groups.Anaero-bic culture bags were used in the hypoxia groups to provide a hypoxic culture,and 5 complex groups were set in each group.The expression levels of HIF-1α and ANGPTL4 in the cells of each group were measured in hypoxic environments.HIF-1α and ANGPTL4 inhibitors were transfected into the cells,placed in an anaerobic culture bag and cultured under hy-poxia for 16 hours.The cells were divided into normal,hypoxia,HIF-1α low expression,and ANGPTL4 low expression groups.Tests measuring cell migration ability,cell permeability,and the expression level of tight junction proteins ZO-1 and occludin were conducted for each group.The cells were also divided into the normal,hypoxia,ANGPTL4 low expres-sion,and WP1066 groups,in which the expression levels of vascular endothelial growth factor(VEGF),p-STAT3,ZO-1 and occludin in each group were measured.Results The retina of rats in the control group had normal morphology,clear structure,and orderly arrangement.The 4w group began to display cell disorders,and as the course of the disease pro-gressed in the 8w and 12w groups,significant increases in retinal damage were observed.A small amount of HIF-1α and ANGPTL4 were expressed in the retina of the control group.As the disease progressed,the expression levels of HIF-1α and ANGPTL4 increased significantly(P<0.05).Compared to the normal group,the expression levels of HIF-1α and ANGPTL4 in each hypoxic group increased significantly as the time spent in hypoxia increased(P<0.05).Compared to the normal group,the cell migration ability,monolayer cell permeability,and expression levels of ZO-1 and occludin in the hypoxia group were significantly enhanced(P<0.05).Compared to the hypoxia group,the cell migration ability,monolayer cell permeability,and ZO-1 and occludin expression levels were significantly reduced in both the HIF-1α low expression and ANGPTL4 low expression groups(P<0.05).There were no significant differences in the cell migration ability,monolayer cell permeability,or expression levels of ZO-1 and occludin between the HIF-1α low expression and the ANGPTL4 low expression groups(P>0.05).Compared to the normal group,the expression levels of ZO-1 and occludin in the hypoxia group were significantly reduced,while the expression levels of VEGF and p-STAT3 were significantly in-creased(P<0.05).Compared to the hypoxia group,in the ANGPTL4 low expression and WP1066 groups,the expression level of ZO-1 and occludin increased significantly,while the expression level of VEGF and p-STAT3 decreased signifi-cantly(P<0.05).Conclusions Inhibition of HIF-1α/ANGPTL4 expression can reduce ARPE-19 cell migration ability and monolayer cell permeability and may be achieved by activating STAT3 phosphorylation.关键词
缺氧诱导因子-1α/血管生成素样蛋白4/人视网膜色素上皮细胞/单层细胞通透性Key words
Hypoxia-inducible factor-1α/angiogenin-like protein 4/Human retinal pigment epithelial cell/Mono-layer cell permeability引用本文复制引用
谌文思,项道满..HIF-1α/ANGPTL4表达变化对ARPE-19细胞迁移和单层细胞通透性的影响及其可能的机制研究[J].临床眼科杂志,2025,33(5):454-459,6.基金项目
广州市科技计划项目重点研发计划(202103000088) （202103000088）
广东省医学科学技术研究基金项目(A2024274) （A2024274）
