Hepcidin is localised in gastric parietal cells, regulates acid secretion and is induced by Helicobacter pylori infection

作者：Peggy Schwarz, Johanna Kübler, Pavel Strnad, Katrin Müller, Thomas F.E. Barth, Andreas Gerloff, Peter Feick, Carole Peyssonnaux, Sophie Vaulont, Guido Adler, Hasan Kulaksiz · 发表于：Gut · 年份：2011 · DOI：10.1136/gut.2011.241208 · 被引用次数：86 · 研究领域：Iron Metabolism and Disorders、Helicobacter pylori-related gastroenterology studies、Drug Transport and Resistance Mechanisms

BACKGROUNDS AND AIMS: Hepcidin is an antimicrobial peptide and the central regulator of iron metabolism. Given that hepcidin was shown to be expressed in a variety of extrahepatic tissues and that stomach plays a role in iron absorption and in defence against infections, this study analysed the importance of hepcidin in the stomach. METHODS: Expression and localisation of gastric hepcidin was studied by quantitative RT-PCR, western blot, immunofluorescence and in situ hybridisation. Regulation of gastric hepcidin expression was analysed both in vitro and in vivo. Hepcidin wild-type (WT) and knockout (KO) animals were used to determine the impact of hepcidin on gastric bacterial overgrowth as well as gastric acid secretion. RESULTS: Hepcidin was abundantly expressed in the gastric fundus and corpus of all tested species. Treatment of AGS cells with ferric nitrilotriacetate solution downregulated hepcidin expression levels, while desferroxamine, interleukin 6 and Helicobacter pylori infection upregulated it. In humans, gastric hepcidin expression was elevated during H pylori infection and normalised after successful eradication. Gastric hepcidin is localised in parietal cells that are indispensable for gastric acid secretion. Comparisons of WT and hepcidin KO mice revealed that acid secretion in hepcidin-deficient mice is markedly reduced and is associated with gastric bacterial overgrowth, expression changes in multiple factors involved in acid secretion (Atp4a, Cck2r,Gas, Sst...