title: Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFκB pathway activation: the use of a novel in vitro model to study epithelial response to infection.
abstract: 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 (NFκB). We hypothesize that NFκB mediates H. pylori-induced Shh.
  
  
  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(+) -ATPase and Shh. H. pylori infection of gastric organoids induced Shh expression; a response that was blocked by inhibiting NFκB 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.
  
  
  CONCLUSIONS
  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 NFκB signaling.
authors.affiliation: Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schumacher
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.forename: Eitaro
authors.initials: E
authors.lastname: Aihara
authors.forename: Amy C
authors.initials: AC
authors.lastname: Engevik
authors.forename: Marshall H
authors.initials: MH
authors.lastname: Montrose
authors.forename: Karen M
authors.initials: KM
authors.lastname: Ottemann
authors.forename: Yana
authors.initials: Y
authors.lastname: Zavros
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D003584:Cytological Techniques / Q000379:methods*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000382:microbiology* / Q000473:pathology*; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000032:analysis; D053823:Hedgehog Proteins / Q000096:biosynthesis*; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D054884:Host-Pathogen Interactions; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D009940:Organoids; D011993:Recombinant Fusion Proteins / Q000032:analysis
chemical_list: D053823:Hedgehog Proteins; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; C465570:Shh protein, mouse; D049452:Green Fluorescent Proteins
keywords: Helicobacter pylori; NF-kB; stomach