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.
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.
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DOI：
10.1111/hel.12152
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发表时间：
2015-02
期刊：
影响因子：
4.4
通讯作者：
Zavros Y
中科院分区：
文献类型：
--
作者：
Schumacher MA;Feng R;Aihara E;Engevik AC;Montrose MH;Ottemann KM;Zavros Y
幽门螺杆菌（H. pylori）感染导致胃中的Sonic Hedgehog（Shh）的急性诱导，其与胃炎的起始相关。H. pylori诱导的Shh尚不清楚。Shh是转录因子核因子-κB（NFκB）的靶基因。我们推测NFκB介导H.幽门诱导的嘘为了观察Shh配体在H. pylori感染的小鼠模型中，我们使用表达融合到绿色荧光蛋白的Shh的小鼠模型（Shh：：GFP小鼠）代替野生型Shh。在体外，Shh表达的变化被测量以响应H。使用从整个分离的胃腺（类器官）生长的三维上皮细胞培养物进行幽门螺杆菌感染。从对照组和表达壁细胞特异性Shh缺失的小鼠（PC-ShhKO小鼠）的胃底区收集的胃产生类器官。感染H后2天内。pylori诱导Shh：：GFP小鼠壁细胞内Shh表达。类器官表达所有主要的胃细胞标志物，包括壁细胞标志物H+，K+-ATP酶和Shh。H. pylori感染胃类器官可诱导Shh表达;这一反应可通过抑制NFκB信号传导而被阻断，并与IκB降解相关。H. pylori感染PC-ShhKO小鼠衍生的类器官没有导致Shh表达的诱导。胃类器官允许研究H。幽门螺杆菌和分化的胃上皮细胞独立于宿主免疫应答。H. pylori诱导壁细胞Shh表达，这是一种通过激活NFκB信号传导介导的反应。
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. 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-dimensonal 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-ShhKO mice). 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-ShhKO mouse-derived organoids did not result in the induction of Shh expression. 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.