Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier
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  • 英文篇名:Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier
  • 作者:Tyler ; J ; Caron ; Kathleen ; E ; Scott ; James ; G ; Fox ; Susan ; J ; Hagen
  • 英文作者:Tyler J Caron;Kathleen E Scott;James G Fox;Susan J Hagen;Department of Surgery,Beth Israel Deaconess Medical Center and Harvard Medical School;Division of Comparative Medicine,Massachusetts Institute of Technology;
  • 英文关键词:Helicobacter pylori;;Tight junction;;Claudins;;Paracellular permeability;;Stomach;;Cytotoxin-associated gene A;;Vacuolating cytotoxin;;Lipopolysaccharide;;Urease;;Ammonia
  • 中文刊名:ZXXY
  • 英文刊名:世界胃肠病学杂志(英文版)
  • 机构:Department of Surgery,Beth Israel Deaconess Medical Center and Harvard Medical School;Division of Comparative Medicine,Massachusetts Institute of Technology;
  • 出版日期:2015-10-28
  • 出版单位:World Journal of Gastroenterology
  • 年:2015
  • 期:v.21
  • 基金:Supported by Department of Surgery funds,BIDMC and NIH No.P30 DK034854(SJH),No.R01 CA093405,No.P30 ES002109,No.R01 OD011141,and No.P01 CA028842(JGF);; NIH No.T32 OD0109978(JGF,to Dr.Caron and Dr.Scott)
  • 语种:英文;
  • 页:ZXXY201540021
  • 页数:17
  • CN:40
  • 分类号:221-237
摘要
Long-term chronic infection with Helicobacter pylori(H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer,tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach,or dysfunction in the infected stomach,however,are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells,claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules,each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging,because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore,the role of H. pylori virulence factors,such as cytotoxin-associated gene A and vacoulating cytotoxin,in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo,likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study,as well,is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions,normally and in H. pylori infection,and make predictions about the consequences of claudin reorganization during H. pylori infection.
        Long-term chronic infection with Helicobacter pylori(H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer,tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach,or dysfunction in the infected stomach,however,are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells,claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules,each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging,because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore,the role of H. pylori virulence factors,such as cytotoxin-associated gene A and vacoulating cytotoxin,in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo,likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study,as well,is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions,normally and in H. pylori infection,and make predictions about the consequences of claudin reorganization during H. pylori infection.
引文
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