Role of ERK activation in H. pylori-induced disruption of cell-cell tight junctions

Sekar, A.; Ho, B.

doi:10.1101/2020.09.03.276600

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bioRxiv · 10.1101/2020.09.03.276600

Role of ERK activation in H. pylori-induced disruption of cell-cell tight junctions

Sekar, A.·Ho, B.

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Abstract

BackgroundTight junctions, a network of claudins and other proteins, play an important role in maintaining barrier function and para-cellular permeability. H. pylori, the major etiological agent of various gastroduodenal diseases, is known to cause tight junction disruption. However, the molecular events that triggered cell-cell tight junction disruption in H. pylori-infected cells, remain largely elusive. Materials and MethodsTrans-epithelial electrical resistance (TEER) and FITC-Dextran permeability measurement were performed to determine the barrier function in H. pylori 88-3887-infected polarized MKN28 cells. For visualization of tight junction protein localization, immunofluorescence and immunoblotting techniques were used. To examine the role of ERK activation in tight junction disruption, U0126, a MEK inhibitor, was employed. To further support the study, computational analyses of H. pylori-infected primary gastric cells were carried out to decipher the transcriptomic changes. ResultsThe epithelial barrier of polarized MKN28 cells when infected with H. pylori displayed disruption of cell-cell junctions as shown by TEER & FITC-dextran permeability tests. Claudin-4 was shown to delocalize from host cytoplasm to nucleus in H. pylori-infected cells. In contrast, delocalization of claudin-4 was minimized when ERK activation was inhibited. Interestingly, transcriptomic analyses revealed the upregulation of genes associated with cell-junction assembly and ERK pathway forming a dense interacting network of proteins. ConclusionTaken together, evidence from this study indicates that H. pylori regulates ERK pathway triggering cell-cell junction disruption, contributing to host pathogenesis. It indicates the vital role of ERK in regulating key events associated with the development of H. pylori-induced gastroduodenal diseases.

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Sekar, A., Ho, B.. 2020-09-03. Role of ERK activation in H. pylori-induced disruption of cell-cell tight junctions. https://doi.org/10.1101/2020.09.03.276600

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