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H elicobacter pylori ‐induced Sonic Hedgehog Expression is Regulated by NF κB Pathway Activation: The Use of a Novel In vitro Model to Study Epithelial Response to Infection
Author(s) -
Schumacher Michael A.,
Feng Rui,
Aihara Eitaro,
Engevik Amy C.,
Montrose Marshall H.,
Ottemann Karen M.,
Zavros Yana
Publication year - 2015
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.12152
Subject(s) - sonic hedgehog , helicobacter pylori , organoid , biology , microbiology and biotechnology , hedgehog signaling pathway , cancer research , gastric mucosa , chemistry , signal transduction , stomach , biochemistry , genetics
Background Helicobacter pylori ( H. pylori ) infection leads to acute induction of Sonic Hedgehog (Shh) in the stomach that is associated with the initiation of gastritis. The mechanism by which H. pylori induces Shh is unknown. Shh is a target gene of transcription factor Nuclear Factor‐κB ( NF κB). We hypothesize that NF κB mediates H. pylori ‐induced Shh. Materials and Methods To visualize Shh ligand expression in response to H. pylori infection in vivo, we used a mouse model that expresses Shh fused to green fluorescent protein (Shh:: GFP mice) in place of wild‐type Shh. In vitro, changes in Shh expression were measured in response to H. pylori infection using 3‐dimensional epithelial cell cultures grown from whole dissociated gastric glands (organoids). Organoids were generated from stomachs collected from the fundic region of control and mice expressing a parietal cell‐specific deletion of Shh ( PC ‐Shh KO mice). Results Within 2 days of infection, H. pylori induced Shh expression within parietal cells of Shh:: GFP mice. Organoids expressed all major gastric cell markers, including parietal cell marker H + ,K + ‐ ATP ase and Shh. H. pylori infection of gastric organoids induced Shh expression; a response that was blocked by inhibiting NF κB signaling and correlated with IκB degradation. H. pylori infection of PC ‐Shh KO mouse‐derived organoids did not result in the induction of Shh expression. Conclusion Gastric organoids allow for the study of the interaction between H. pylori and the differentiated gastric epithelium independent of the host immune response. H. pylori induces Shh expression from the parietal cells, a response mediated via activation of NF κB signaling.