title: Gastric Helicobacter infection induces iron deficiency in the INS-GAS mouse.
abstract: There is increasing evidence from clinical and population studies for a role of H. pylori infection in the aetiology of iron deficiency. Rodent models of Helicobacter infection are helpful for investigating any causal links and mechanisms of iron deficiency in the host. The aim of this study was to investigate the effects of gastric Helicobacter infection on iron deficiency and host iron metabolism/transport gene expression in hypergastrinemic INS-GAS mice. INS-GAS mice were infected with Helicobacter felis for 3, 6 and 9 months. At post mortem, blood was taken for assessment of iron status and gastric mucosa for pathology, immunohistology and analysis of gene expression. Chronic Helicobacter infection of INS- GAS mice resulted in decreased serum iron, transferrin saturation and hypoferritinemia and increased Total iron binding capacity (TIBC). Decreased serum iron concentrations were associated with a concomitant reduction in the number of parietal cells, strengthening the association between hypochlorhydria and gastric Helicobacter-induced iron deficiency. Infection with H. felis for nine months was associated with decreased gastric expression of iron metabolism regulators hepcidin, Bmp4 and Bmp6 but increased expression of Ferroportin 1, the iron efflux protein, iron absorption genes such as Divalent metal transporter 1, Transferrin receptor 1 and also Lcn2 a siderophore-binding protein. The INS-GAS mouse is therefore a useful model for studying Helicobacter-induced iron deficiency. Furthermore, the marked changes in expression of gastric iron transporters following Helicobacter infection may be relevant to the more rapid development of carcinogenesis in the Helicobacter infected INS-GAS model.
authors.affiliation: Molecular Gastroenterology, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, United Kingdom.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Thomson
authors.forename: D Mark
authors.initials: DM
authors.lastname: Pritchard
authors.forename: Sally A
authors.initials: SA
authors.lastname: Boxall
authors.forename: Abdul A
authors.initials: AA
authors.lastname: Abuderman
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Williams
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
authors.forename: Jean E
authors.initials: JE
authors.lastname: Crabtree
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D018798:Anemia, Iron-Deficiency / Q000150:complications / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D005755:Gastrins / Q000235:genetics; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D044922:Helicobacter felis / Q000378:metabolism* / Q000472:pathogenicity; D064451:Hepcidins; D007328:Insulin / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D027682:Cation Transport Proteins; D005755:Gastrins; D064451:Hepcidins; D007328:Insulin; D007501:Iron; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011990:Receptors, Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C525810:Bmp4 protein, mouse; C525817:Bmp6 protein, mouse; C579599:Hamp protein, mouse; C480029:Tfrc protein, mouse; C071332:Lcn2 protein, mouse