Disruption of the Epithelial Apical-Junctional Complex by Helicobacter pylori CagA

Abstract

Helicobacter pylori translocates the protein CagA into gastric epithelial cells and has been linked to peptic ulcer disease and gastric carcinoma. We show that injected CagA associates with the epithelial tight-junction scaffolding protein ZO-1 and the transmembrane protein junctional adhesion molecule, causing an ectopic assembly of tight-junction components at sites of bacterial attachment, and altering the composition and function of the apical-junctional complex. Long-term CagA delivery to polarized epithelia caused a disruption of the epithelial barrier function and dysplastic alterations in epithelial cell morphology. CagA appears to target H.pylori to host cell intercellular junctions and to disrupt junction-mediated functions.

Tight junction-based epithelial microenvironment and cell proliferation

“…Some kinds of bacterial infection and inflammation are closely related to epithelial cell proliferation. When a bacterial infection, such as H. pylori, is established in epithelia, TJs are disrupted and disappear, leading to invasion of the bacterial components and/or toxin from the apical to the lateral sides of epithelial cells to induce inflammation and cell proliferation of epithelial cells (Amieva et al, 2003). In addition, when some inflammation-inducing substances penetrate through the paracellular TJ-based barriers, inflammation could take place with epithelial cell proliferation.…”

Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA

“…CagA colocalizes with tight junction proteins such as ZO-1 and JAM and causes disruption of the tight junction in polarized epithelial cells in a manner that is independent of CagA tyrosine phosphorylation (Amieva et al, 2003). As a result, epithelial cells expressing CagA lose cell polarity, which is concomitantly associated with pseudopodia formation and degradation of the basement membrane (Bagnoli et al, 2005).…”

Helicobacter pylori eradication: Novel therapy for immune thrombocytopenic purpura? A review of the literature

“…H. pylori is then capable of inducing the secretion of substances from the host cell that promote inflammation and induce host cell apoptosis [81]. Importantly, the expression of a specific genomic fragment, the cag pathogenicity island (cag-PAI), evokes a profound cytokine and growth factor response from the host cell [82,83]. Chemokinemediated attraction of cells including T lymphocytes (predominately Th1), B lymphocytes, plasma cells, macrophages, and neutrophils follows.…”