Published online Oct 28, 2015. doi: 10.3748/wjg.v21.i40.11411
Peer-review started: May 14, 2015
First decision: June 2, 2015
Revised: June 26, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: October 28, 2015
Processing time: 164 Days and 23.2 Hours
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.
Core tip: Tight junction dysfunction is a risk factor for cancer development during Helicobacter pylori (H. pylori) infection. The recent identification of numerous barrier-forming claudins has greatly improved our understanding of properties that regulate selective permeation across the tight junction in general, but little is known about the role of claudins in the stomach, or in H. pylori infection. In this article, we review the current state of knowledge on stomach tight junction composition and organization, discuss the details of claudin expression in various species and in cultured gastric cells, and discuss the implications of tight junction dysregulation in gastric cancer pathogenesis.