中国现代医学杂志2016，Vol.26Issue(5)：1-6,6.DOI:10.3969/j.issn.1005-8982.2016.05.001
肝X受体激动剂上调人肾小球内皮细胞血栓调节蛋白表达的机制和作用
Mechanism and role of LXR agonist upregulating thrombo-modulin expression in human glomerular endothelial cells
摘要
Abstract
Objective To explore the effect of liver X receptor (LXR) agonist T0901317 on thrombomodulin (TM) expression in human glomerular endothelial cells (HUGECs) and its mechanism. Methods Western blot was used to detect the expressions of IκBα, p-IκBα, nuclear transcription factor-κB (NF-κβ) p65 and p-NF-κB p65 in HUGECs stimulated by 25 mmol high glucose and 2μmol T0901317. The interaction between LXR and the transcriptional coactivator p300 in HUGECs was detected using co-immunoprecipitation (Co-IP) assay. The concentrations of IL-1β and TNF-α in the supernatant of HUGECs transfected with or without AdTMshRNA were determined using commercially available ELISA kits. Results T0901317 (2 μmol) significantly reduced the phosphorylation of IκBα and NF-κB p65 in the HUGECs stimulated by high glucose ( <0.05). The activity of NF-κB was increased by LXR-α silencing despite the presence of T0901317. Co-IP revealed up-regulation of LXP and p300 in the HUGECs 24 h after stimulation by 2μmol T0901317. T0901317 inhibited the secretion of high glucose-induced inflammatory cytokines such as TNF-α and IL-1β in the HUGECs ( <0.05). The levels of TNF-α and IL-1β were increased by TM silencing with AdTMshRNA despite the presence of T0901317, but the differences were not significant ( >0.05). Conclusions LXR agonist increases TM expression and inhibits secretion of inflammatory mediators probably by competitively blocking the interaction between NF-κB and p300 through interaction with p300.关键词
人肾小球内皮细胞/肝X受体/血栓调节蛋白/核转录因子-κBKey words
glomerular endothelial cell/liver X receptor/thrombomodulin/nuclear transcription factor-κB分类
医药卫生引用本文复制引用
丁涵露,李怡,冯韵霖,陈瑾,钟翔,王楠,汪伟,张萍,王莉..肝X受体激动剂上调人肾小球内皮细胞血栓调节蛋白表达的机制和作用[J].中国现代医学杂志,2016,26(5):1-6,6.基金项目
国家自然科学基金（No81170680）；四川省科技厅课题 （）
