空军军医大学学报2024,Issue(3) :246-250.DOI:10.13276/j.issn.2097-1656.2024.03.002

胆汁酸通过调控HOXB7促进胃黏膜肠化生

Bile acid promotes gastric intestinal metaplasia by regulating HOXB7

林可昕 姚诺 赵行雨 曲晓东 李学志 李嵩博 董强 王娜 时永全
空军军医大学学报2024,Issue(3) :246-250.DOI:10.13276/j.issn.2097-1656.2024.03.002

胆汁酸通过调控HOXB7促进胃黏膜肠化生

Bile acid promotes gastric intestinal metaplasia by regulating HOXB7

林可昕 1姚诺 1赵行雨 1曲晓东 1李学志 1李嵩博 1董强 1王娜 1时永全1
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作者信息

  • 1. 国家消化系统疾病临床医学研究中心, 消化系肿瘤整合防治全国重点实验室, 空军军医大学西京消化病医院, 陕西 西安 710032
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摘要

目的 探究 HOXB7 在胆汁酸诱导的胃黏膜肠化生(GIM)中的作用.方法 利用 qRT-PCR 和Western blotting检测HOXB7 及多种肠型标志分子在不同细胞系和黏膜组织中的表达水平.借助过表达质粒及特异性siRNA转染分别建立HOXB7 过表达和敲低细胞模型,并检测肠型标志分子的表达变化.结果 在胃上皮细胞GES-1 中,脱氧胆酸(DCA)以时间依赖和浓度依赖的方式诱导HOXB7 和肠型标志分子CDX2、MUC2 的表达上调(P<0.01).HOXB7 在多种胃癌细胞系及正常肠上皮细胞系中的表达水平远高于GES-1(P<0.01).HOXB7在小鼠大肠黏膜组织中的表达水平显著高于食管和胃黏膜组织(P<0.05),呈吻尾轴表达模式.HOXB7 在GIM患者肠化生组织中的表达水平显著高于配对正常胃黏膜组织(P<0.01).HOXB7 能够调控肠型标志分子CDX2、KLF4 和MUC2 在胃上皮细胞系中的表达(P<0.05,P<0.01),而敲低HOXB7 能减弱DCA对多种肠型标志分子的表达诱导作用(P<0.01).结论 HOXB7 参与了胆汁酸对GIM的诱导调控,深入揭示HOXB7 的上下游分子通路有助于寻找新的GIM防治靶点.

Abstract

Objective To investigate the effect of HOXB7 in gastric intestinal metaplasia(GIM)induced by bile acid.Methods qRT-PCR and Western blotting were used to detect the expression levels of HOXB7 and several intestinal markers in different cell lines and mucosal tissues.HOXB7 overexpressing and knock-down cell models were established with overexpressing plasmid and specific siRNA transfection,and the expression changes of intestinal markers were detected.Results In gastric epithelial cell GES-1,deoxycholic acid induced the up-regulation of the expression of HOXB7 and intestinal markers such as CDX2 and MUC2 in a time-dependent and concentration-dependent manner(P<0.01).The expression level of HOXB7 was significantly higher in several gastric cancer cell lines and normal intestinal mucosal cell lines than that in GES-1(P<0.01).The expression level of HOXB7 in mouse large intestinal mucosa was significantly higher than that in esophageal and gastric mucosa(P<0.05),showing an expression pattern along the anterior-posterior axis.The expression level of HOXB7 was significantly higher in GIM tissues of GIM patients than that in paired normal mucosa(P<0.01).HOXB7 could regulate the expression of intestinal markers such as CDX2,KLF4 and MUC2 in gastric epithelial cell lines(P<0.05,P<0.01),while knock-down of HOXB7 could reduce the expression of intestinal markers induced by deoxycholic acid(P<0.01).Conclusion HOXB7 is involved in the induction and regulation of GIM induced by bile acid.In-depth understanding of the upstream and downstream molecular pathways of HOXB7 is helpful to find new targets for the prevention and treatment of GIM.

关键词

胃黏膜肠化生/胆汁酸/HOXB7

Key words

gastric intestinal metaplasia/bile acid/HOXB7

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基金项目

国家自然科学基金(82170560)

国家自然科学基金(82200567)

出版年

2024
空军军医大学学报
第四军医大学

空军军医大学学报

CHSSCD
影响因子:0.372
ISSN:2097-1656
参考文献量18
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