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Helicobacter pylori Induces Vascular Endothelial Growth Factor Production in Gastric Epithelial Cells Through Hypoxia‐Inducible Factor‐1α‐Dependent Pathway
Author(s) -
Kang MinJung,
Song EunJung,
Kim BoYeon,
Kim DongJae,
Park JongHwan
Publication year - 2014
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/hel.12169
Subject(s) - helicobacter pylori , vascular endothelial growth factor , hypoxia inducible factors , secretion , biology , signal transduction , microbiology and biotechnology , gastric mucosa , cancer research , stomach , endocrinology , biochemistry , vegf receptors , genetics , gene
Abstract Background Although Helicobacter pylori have been known to induce vascular endothelial growth factor ( VEGF ) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori ‐infected gastric epithelial cells. Materials and methods We evaluated production of VEGF , activation of nuclear factor nuclear factor‐kappaB ( NF ‐κB) and mitogen‐activated protein kinases ( MAPK s) and hypoxia‐inducible factor‐1α ( HIF ‐1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4 SS ). Results H. pylori induced VEGF production in gastric epithelial cells via both T4 SS ‐dependent and T4 SS ‐independent pathways, although T4 SS ‐independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF ‐κB and MAPK s is dispensable for H. pylori ‐induced VEGF production in gastric epithelial cells. H. pylori led to HIF ‐1α stabilization in gastric epithelial cells independently of T4 SS , NF ‐κB, and MAPK s, which was essential for VEGF production in these cells. N‐acetyl‐cysteine ( NAC ), a reactive oxygen species ( ROS ) inhibitor, treatment impaired H. pylori ‐induced HIF ‐1α stabilization and VEGF production in gastric epithelial cells. Conclusion We defined the important role of ROS ‐ HIF ‐1α axis in VEGF production of H. pylori ‐infected gastric epithelial cells, and bacterial T4 SS has a minor role in H. pylori ‐induced VEGF production of gastric epithelial cells.