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. Issue 1 (11th December 2014)

• Record Type: Journal Article
• Authors: Schumacher, Michael A.; Feng, Rui; Aihara, Eitaro; Engevik, Amy C.; Montrose, Marshall H.; Ottemann, Karen M.; Zavros, Yana
• Is Part Of: Helicobacter. Volume 20:Issue 1(2015:Feb.)
• Page Start: 19
• Page End: 28
• Publication Date: 2014-12-11
• Subjects: Helicobacter -- Periodicals; Helicobacter infections -- Periodicals; Stomach -- Diseases -- Periodicals; 616.3301405
• DOI: 10.1111/hel.12152
• Languages: English
• ISSNs: 1083-4389

Abstract

<abstract abstract-type="main" id="hel12152-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="hel12152-sec-0001" sec-type="section"> <title>Background</title> <p> <italic>Helicobacter pylori</italic> (<italic>H. pylori</italic>) infection leads to acute induction of Sonic Hedgehog (Shh) in the stomach that is associated with the initiation of gastritis. The mechanism by which <italic>H. pylori</italic> induces Shh is unknown. Shh is a target gene of transcription factor Nuclear Factor‐κB (NFκB). We hypothesize that NFκB mediates <italic>H. pylori</italic>‐induced Shh.</p> </sec> <sec id="hel12152-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>To visualize Shh ligand expression in response to <italic>H. pylori</italic> 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 <italic>H. pylori</italic> 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<sup>KO</sup> mice).</p> </sec> <sec id="hel12152-sec-0003" sec-type="section"> <title>Results</title> <p>Within 2 days of infection, <italic>H. pylori</italic> induced Shh expression within parietal cells of Shh::GFP mice. Organoids expressed all major gastric cell markers, including parietal cell marker H<sup>+</sup>, K<sup>+</sup>‐ATPase and Shh. <italic>H. pylori</italic> infection of gastric organoids induced Shh expression; a response that was blocked by inhibiting NFκB signaling and correlated with IκB degradation. <italic>H. pylori</italic> infection of PC‐Shh<sup>KO</sup> mouse‐derived organoids did not result in the induction of Shh expression.</p> </sec> <sec id="hel12152-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Gastric organoids allow for the study of the interaction between <italic>H. pylori</italic> and the differentiated gastric epithelium independent of the host immune response. <italic>H. pylori</italic> induces Shh expression from the parietal cells, a response mediated via activation of NFκB signaling.</p> </sec> </abstract>