新医学2017,Vol.48Issue(7):455-460,6.DOI:10.3969/j.issn.0253-9802.2017.07.005
活化转录因子4参与高糖诱导的人视网膜微血管内皮细胞炎症
Effect of activation transcription factor-4 on high glucose-induced inflammatory response of human retinal microvascular endothelial cells
摘要
Abstract
Objective To evaluate the effect and mechanism of activation transcription factor-4 (ATF4) upon the inflammatory response of human retinal endothelial cells (HRMECs) induced by high glucose.Methods All HRMECs were assigned into the normal glucose (5.5 mmol/L D-glucose),high glucose (25 mmol/L D-glucose),control (5.5 mmol/L D-glucose+19.5 mmol/L mannitol),high glucose+ATF4 interfere and high glucose+ Scrambled groups.Intervention of high glucose or mannitol was endured for 24 h.The expression of ATF4 protein in HRMECs was interfered by ribonucleic acid interfere technique.The expression levels of ATF4,TNF-α,intercellular adherence molecule-1 (ICAM-1),IL-1β,phosphorylated nuclear transcription factor-κB p65 (p-NF-κB p65) were measured by western blot.The status of nucleus translocation of NF-κB p65 was observed under confocal laser scanning microscopy.Results Compared with the normal glucose group,the expression levels of ATF4,TNF-α,ICAM-1,IL-1β and p-NF-κB p65 were significantly up-regulated in the high glucose group (all P<0.05).No statistical significance was identified in the expression levels of ATF4 and inflammatory cytokines between the control and normal glucose groups(all P>0.05).Compared with the high glucose+Scrambled group,the expression of ATF4 and inflammatory cytokines was remarkably down-regulated in the high glucose+ATF4 interfere group (all P<0.05).Compared with the high glucose group,the nucleus translocation of NF-κB p65 was moderately weakened in the high glucose+ATF4 interfere group.Conclusions High glucose can induce the incidence of inflammatory response of HRMECs and promote the nucleus translocation of NF-κB p65.Therefore,down-regulating the expression of ATF4 is able to attenuate the high glucose-induced inflammatory response and nucleus translocation of NF-κB p65,prompting that ATF4 plays a pivotal role in the inflammatory response of HRMECs induced by high glucose,which can be achieved by regulating the activation of NF-κB p65.关键词
人视网膜微血管内皮细胞/炎症反应/活化转录因子4/核转录因子-κBp65/糖尿病视网膜病变Key words
Human retinal endothelial cell/Inflammatory response/Activation transcription factor-4/Nuclear transcription factor-κB p65/Diabetic retinopathy引用本文复制引用
王琪,周丽,李静仁,朱碧连,唐喜香,陈燕铭..活化转录因子4参与高糖诱导的人视网膜微血管内皮细胞炎症[J].新医学,2017,48(7):455-460,6.基金项目
广东省科技发展专项资金(协同创新与平台环境建设方向)项目(2016A050502010) (协同创新与平台环境建设方向)
中山大学临床医学研究5010计划临床研究常规项目(2015015) (2015015)
广州市科技科学研究专项(2060404) (2060404)