解放军医学院学报2024，Vol.45Issue(1)：78-83,封3,7.DOI:10.12435/j.issn.2095-5227.2024.013
前列腺素E2介导的EP4受体通路通过抑制内质网应激减轻溃疡性结肠炎黏膜损伤的研究
PGE2/EP4 signaling pathway attenuates mucosal damage in ulcerative colitis by inhibiting endoplasmic reticulum stress
摘要
Abstract
Background PGE2/EP4 signaling pathway can alleviate mucosal damage in ulcerative colitis,but the mechanism of its regulation of endoplasmic reticulum stress is not fully understood.Objective To clarify the mechanism of PGE2/EP4 signaling pathway in regulating ER stress in mucosal injury in ulcerative colitis(UC).Methods Firstly,divide the mice into a model group and a control group,and detect the expression level of EP4 through immunohistochemistry and PCR,by constructing mice UC model,the experimental mice were divided into acute UC group(DSS),PGE2-treated group(DSS + PGE2),indomethacin treatment group(DSS + indomethacin),and control group.The disease activity index of mice was observed and recorded.The colonic mucosal tissues were collected to detect the levels of EP4 and GRP78,epithelial cell apoptosis and proliferation after PGE2 treatment.The expression of β-arrestin1 was downregulated by siRNA in HCT116 cells,then the expression of GRP78 was detected by PGE2 treatment.Results EP4 levels decreased and GRP78 levels increased in the colon mucosa of acute UC mice(P<0.05).After PGE2 treatment,the colon mucosal epithelial cells showed apoptosis,and the UC disease activity index decreased significantly(P<0.05),while EP4 levels and the level of intestinal epithelial cell proliferation increased significantly(P<0.05).The protein level of GRP78 in UC colon mucosa of mice were increased,and it decreased significantly after PGE2 administration.After knocking down the expression of β-arrestin1by siRNA in HCT116 cells,the expression level of GRP78 was significantly up-regulated(P<0.05).Conclusion PGE2/EP4 signaling pathway attenuates mucosal injury by inhibiting endoplasmic reticulum stress signaling in colitis,which inhibits epithelial cell apoptosis and promotes its proliferation.关键词
溃疡性结肠炎/内质网应激/PGE2/EP4信号通路/炎症/黏膜损伤Key words
ulcerative colitis/endoplasmic reticulum stress/PGE2/EP4 signaling pathway/inflammation/mucosal injury分类
医药卫生引用本文复制引用
彭小婕,张昌越,周代超,吕志武..前列腺素E2介导的EP4受体通路通过抑制内质网应激减轻溃疡性结肠炎黏膜损伤的研究[J].解放军医学院学报,2024,45(1):78-83,封3,7.基金项目
深圳市科技计划项目(JCYJ20180305123709909) （JCYJ20180305123709909）
