Abstract
BackgroundThe pathogenesis of Helicobacter pylori (H. pylori) infection-induced duodenal ulcer remains to be elucidated. Duodenal mucosal bicarbonate secretion is the most important protective factor against acid-induced mucosal injury. We previously revealed that H. pylori infection downregulated the expression and functional activity of duodenal mucosal cystic fibrosis transmembrane conductance regulator (CFTR) and solute linked carrier 26 gene family A6 (SLC26A6) which are the two key duodenal mucosal epithelial cellular bicarbonate transporters to mediate duodenal bicarbonate secretion. In this study, we investigated the mechanism of H. pylori infection-induced duodenal CFTR and SLC26A6 expression downregulation.ResultsWe found that H. pylori infection induced the increase of serum transforming growth factor β (TGFβ) level and duodenal mucosal TGFβ expression and the decrease of duodenal mucosal CFTR and SLC26A6 expressions in C57 BL/6 mice. The results from the experiments of human duodenal epithelial cells (SCBN) showed that H. pylori increased TGFβ production and decreased CFTR and SLC26A6 expressions in SCBN cells. TGFβ inhibitor SB431542 reversed the H. pylori-induced CFTR and SLC26A6 expression decreases. The further results showed that TGFβ directly decreased CFTR and SLC26A6 expressions in SCBN cells. TGFβ induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and P38 MAPK inhibitor SB203580 reversed the TGFβ-induced CFTR and SLC26A6 expression decreases.ConclusionsH. pylori infection downregulates duodenal epithelial cellular CFTR and SLC26A6 expressions through TGFβ-mediated P38 MAPK signaling pathway, which contributes to further elucidating the pathogenesis of H. pylori-associated duodenal ulcer.
Highlights
The pathogenesis of Helicobacter pylori (H. pylori) infection-induced duodenal ulcer remains to be elucidated
We previously showed that H. pylori infection downregulated the expression and functional activity of duodenal mucosal cystic fibrosis transmembrane conductance regulator (CFTR) and solute linked carrier 26 gene family A6 (SLC26A6) [13], which contributes to the development of duodenal ulcer
transforming growth factor β (TGFβ) inhibitor SB431542 (10 μM) reversed H. pylori-induced CFTR and SLC26A6 protein expression decreases in SCBN cells (Fig. 4). These results indicate that H. pylori infection downregulates duodenal epithelial cellular CFTR and SLC26A6 expressions through TGFβ signaling
Summary
The pathogenesis of Helicobacter pylori (H. pylori) infection-induced duodenal ulcer remains to be elucidated. Duodenal mucosal bicarbonate secretion is the most important protective factor against acid-induced mucosal injury. We investigated the mechanism of H. pylori infectioninduced duodenal CFTR and SLC26A6 expression downregulation. It has been demonstrated that Helicobacter pylori (H. pylori) infection is main etiologic agent responsible for duodenal ulcerogenesis [1, 3, 4]. In spite of extensive studies, the pathogenesis of H. pylori infection-induced duodenal ulcer remains to be elucidated. Duodenal mucosal bicarbonate secretion is the most important protective factor against acid-induced. A (VacA)-positive H. pylori strains [9] These studies suggest that the effect of H. pylori on duodenal mucosal bicarbonate secretion might be involved in the pathogenesis of H. pylori-associated duodenal ulcer. The mechanisms whereby H. pylori influences duodenal mucosal bicarbonate secretion are not completely understood
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