Clathrin‐coated pit endocytosis and Rho Kinase mediate Helicobacter pylori‐induced claudin‐4 disruption in human gastric epithelial cells
Bibliographic record
Abstract
The ability of H. pylori (Hp) to disrupt the gastric epithelial barrier may contribute to the development of gastroduodenal ulcers and gastric adenocarcinomas. The direct effects of Hp on the gastric epithelium remain incompletely understood. Internalization of TJ proteins promotes the rapid loss of intercellular adhesion and a subsequent increase in epithelial permeability. Aim : The aim of this study was to investigate the mechanisms involved in Hp‐induced disruption of epithelial barrier structure and function in vitro using the human gastric epithelial (HGE‐20) cell line. Results : Hp strain SS1 significantly increased transepithelial fluxes of FITC‐dextran. Immunocytochemistry and western blotting demonstrated golgi apparatus‐associated accumulation of claudin‐4 in the cytoplasm, which coincided with the loss of claudin‐4 from the cell membrane. Pharmacological inhibition of de novo protein synthesis as well as the blocking of clathrin‐coated pit endocytosis prevented these effects. Infection with Hp also increased Rho kinase expression and activity, and inhibition of Rho kinase reduced loss of claudin‐4 from the membrane. Conclusion : The mechanisms by which Hp disrupts the gastric epithelial barrier involve membrane‐to‐cytosol translocation of claudin‐4. This effect is mediated by clathrin‐coated pit endocytosis and depends, at least in part, on Rho kinase. This work was funded by the CIHR.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".