@article {Sekar2020.09.03.276600, author = {Amita Sekar and Bow Ho}, title = {Role of ERK activation in H. pylori-induced disruption of cell-cell tight junctions}, elocation-id = {2020.09.03.276600}, year = {2020}, doi = {10.1101/2020.09.03.276600}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Background Tight 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 Methods Trans-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.Results The 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.Conclusion Taken 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.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2020/09/03/2020.09.03.276600}, eprint = {https://www.biorxiv.org/content/early/2020/09/03/2020.09.03.276600.full.pdf}, journal = {bioRxiv} }