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Fig. 3 | Cell Communication and Signaling

Fig. 3

From: From inflammation to gastric cancer – the importance of Hedgehog/GLI signaling in Helicobacter pylori-induced chronic inflammatory and neoplastic diseases

Fig. 3

Model of H. pylori interference with the SHH signaling pathway. a Infection with H. pylori induces a loss of SHH-expressing parietal cells (1). Loss of SHH might involve H. pylori-induced CDX2 expression, which then binds the SHH gene promoter leading to SHH downregulation (2) and to a dysfunction of parietal cells (8). Downregulation of SHH has also been associated with hypermethylation of the promoters of hedgehog signaling genes (3). The negative effect of H. pylori on SHH expression involves NF-κB activity (4) that induces the expression of cytokines to reduce SHH gene expression (5). On the other hand, SHH can be upregulated in response to calcium and PKC activity (11), which leads to the activation of GLI expression to enhance schlafen-4 (6) or increases H+/K+-ATPase gene expression (10). A positive effect of SHH on cytokine expression was observed (7), which could contribute to the NF-κB responses. H. pylori-induced proinflammatory cytokines further the dysfunction of parietal cells to inhibit gastric acid production (9), while an increased SHH expression promotes anti-apoptotic effect and proliferation (12). b H. pylori-increased SHH can function as a chemoattractant for macrophages and BM-MSCs. IFNγ-induced MSC proliferation required SHH secretion via an autocrine regulatory mechanism and appears to be involved in the repopulation of the inflamed tissue

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