胆汁酸通过调控 HOXB7 促进胃黏膜肠化生  被引量:2

Bile acid promotes gastric intestinal metaplasia by regulating HOXB7

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作  者:林可昕 姚诺 赵行雨 曲晓东 李学志 李嵩博 董强 王娜 时永全 LIN Kexin;YAO Nuo;ZHAO Xingyu;QU Xiaodong;LI Xuezhi;LI Songbo;DONG Qiang;WANG Na;SHI Yongquan(State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,National Clinical Research Center for Digestive Diseases,Xijing Hospital of Digestive Diseases,Air Force Medical University,Xi an 710032,China)

机构地区:[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

出  处:《空军军医大学学报》2024年第3期246-250,共5页Journal of Air Force Medical University

基  金:国家自然科学基金(82170560,82200567)。

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。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 

分 类 号:R735.2[医药卫生—肿瘤]

 

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