Effects of Helicobacter pylori Infection on Gastric Parietal Cells and E-cadherin in Mongolian Gerbils

Murakami, Motonobu; Fukuzawa, Mayu; Yamamoto, Mika; K, Hamaya; Tamura, Yuumi; Sugiyama, Akiko; Takahashi, Rei; Murakami, Toshiko; Amagase, Kikuko; Takeuchi, Koji

doi:10.1254/jphs.12191fp

Cited by 7 publications

(6 citation statements)

References 36 publications

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“…This relationship was statistically significant even when uninfected animals were excluded from the analysis. Previous studies have shown that H. pylori infection can lead to the loss of parietal cells (acid-secreting cells found in the stomach) in Mongolian gerbils as well as atrophic gastritis and parietal cell loss in humans (33,57). Similarly, infected gerbils in the current study exhibited parietal cell loss, whereas uninfected gerbils did not ( Fig.…”

Section: Fig 2 Reduced Serum Ferritin Levels In H Pylori-infected Gesupporting

confidence: 69%

Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

et al. 2016

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Epidemiologic studies have provided conflicting data regarding an association between Helicobacter pylori infection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role of H. pylori infection, as well as a possible role of diet, in H. pylori-associated IDA. Mongolian gerbils (either H. pylori infected or uninfected) received a normal diet or one of three diets associated with increased H. pylori virulence: high-salt, low-iron, or a combination of a high-salt and low-iron diet. In an analysis of all infected animals compared to uninfected animals (independent of diet), H. pylori-infected gerbils had significantly lower hemoglobin values than their uninfected counterparts at 16 weeks postinfection (P < 0.0001). The mean corpuscular volume (MCV) and serum ferritin values were significantly lower in H. pylori-infected gerbils than in uninfected gerbils, consistent with IDA. Leukocytosis and thrombocytosis were also detected in infected gerbils, indicating the presence of a systemic inflammatory response. In comparison to uninfected gerbils, H. pylori-infected gerbils had a higher gastric pH, a higher incidence of gastric ulcers, and a higher incidence of fecal occult blood loss. Anemia was associated with the presence of gastric ulceration but not gastric cancer. Infected gerbils consuming diets with a high salt content developed gastric ulcers significantly more frequently than gerbils consuming a normal-salt diet, and the lowest hemoglobin levels were in infected gerbils consuming a high-salt/low-iron diet. These data indicate that H. pylori infection can cause IDA and that the composition of the diet influences the incidence and severity of H. pylori-induced IDA.A nemia affects up to 1.6 billion people worldwide, potentially resulting in fatigue, decreased productivity, increased susceptibility to infection, or death (1-5). A wide variety of infectious processes can be primary causes of anemia or can exacerbate anemia arising from noninfectious etiologies. For example, intestinal parasitic infections can cause chronic blood loss, leading to iron deficiency anemia (IDA; i.e., anemia due to iron deficiency) (3, 6). Anemia arises in patients with malaria because the parasites invade erythrocytes (2), and bacterial toxins can cause hemolysis (7). In addition, chronic infections, chronic immune activation, and cancer can cause a form of anemia known as "anemia of chronic disease" (8).Colonization of the human stomach with the gastric bacterium Helicobacter pylori is another potential cause of anemia. Anemia often occurs in the setting of symptomatic H. pylori-associated diseases (peptic ulcer disease or gastric cancer), but it has been suggested that H. pylori may also be a cause of IDA in asymptomatic persons with no evidence of peptic ulcer disease or gastric cancer (9). H. pylori has been linked to several other hematologic diseases, including pernicious anemia (vitamin B 12 deficiency arising through an autoimmune-mediated process) and idiopathic throm...

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Section: Fig 2 Reduced Serum Ferritin Levels In H Pylori-infected Gesupporting

confidence: 69%

Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

et al. 2016

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“…Other gastric Helicobacter species, including H. pylori , H. heilmannii , and H. felis , have been described to cause massive parietal cell loss in rodent models, leading to the deregulation of gastric morphology and the development of intestinal metaplasia [ 39 – 41 ]. Most likely, the development of gastritis in the corpus region, which is more pronounced compared to H. suis infection in these same animal models, contributes largely to this massive loss of parietal cells.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter suis affects the health and function of porcine gastric parietal cells

Zhang

Ducatelle

Mihi

et al. 2016

Vet Res

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The stomach of pigs at slaughter age is often colonized by Helicobacter (H.) suis, which is also the most prevalent gastric non-H. pylori Helicobacter (NHPH) species in humans. It is associated with chronic gastritis, gastric ulceration and other gastric pathological changes in both hosts. Parietal cells are highly specialized, terminally differentiated epithelial cells responsible for gastric acid secretion and regulation. Dysfunction of these cells is closely associated with gastric pathology and disease. Here we describe a method for isolation and culture of viable and responsive parietal cells from slaughterhouse pigs. In addition, we investigated the interactions between H. suis and gastric parietal cells both in H. suis-infected six-month-old slaughter pigs, as well as in our in vitro parietal cell model. A close interaction of H. suis and parietal cells was observed in the fundic region of stomachs from H. suis positive pigs. The bacterium was shown to be able to directly interfere with cultured porcine parietal cells, causing a significant impairment of cell viability. Transcriptional levels of Atp4a, essential for gastric acid secretion, showed a trend towards an up-regulation in H. suis positive pigs compared to H. suis-negative pigs. In addition, sonic hedgehog, an important factor involved in gastric epithelial differentiation, gastric mucosal repair, and stomach homeostasis, was also significantly up-regulated in H. suis positive pigs. In conclusion, this study describes a successful approach for the isolation and culture of porcine gastric parietal cells. The results indicate that H. suis affects the viability and function of this cell type.

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“…The parietal cells destruction found in AMAG combined with the important role of E-cadherin in epithelial polarity and gastric glandular architecture, suggests that germline alterations of CDH1 could be an additional risk factor for GC development in AMAG patient [31].…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of CDH1 Germline Variants in Sporadic Gastric Cancer Patients and in Individuals at Risk of Gastric Cancer

et al. 2013

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ObjectiveTo screen and characterize germline variants for E-cadherin (CDH1) in non-hereditary gastric cancer (GC) patients and in subjects at risk of GC.Methods59 GCs, 59 first degree relatives (FDRs) of GC, 20 autoimmune metaplastic atrophic gastritis (AMAGs) and 52 blood donors (BDs) were analyzed for CDH1 by direct sequencing, structural modelling and bioinformatics. Functional impact on splicing was assessed for intronic mutations. E-cadherin/β-catenin immunohistochemical staining and E-cadherin mRNA quantification using RT-PCR were performed.ResultsIn GCs, 4 missense variants (p.G274S; p.A298T; p.T470I; p.A592T), 1 mutation in the 5′UTR (−71C>G) and 1 mutation in the intronic IVS12 (c.1937-13T>C) region were found. First pathogenic effect of p.A298T mutation was predicted by protein 3D modelling. The novel p.G274S mutation showed a no clear functional significance. Moreover, first, intronic IVS12 (c.1937-13T>C) mutation was demonstrated to lead to an aberrant CDH1 transcript with exon 11 deletion. This mutation was found in 2 GCs and in 1 BD. In FDRs, we identified 4 variants: the polymorphic (p.A592T) and 3 mutations in untranslated regions with unidentified functional role except for the 5′UTR (−54G>C) that had been found to decrease CDH1 transcription. In AMAGs, we detected 2 alterations: 1 missense (p.A592T) and 1 novel variant (IVS1 (c.48+7C>T)) without effect on CDH1 splicing. Several silent and polymorphic substitutions were found in all the groups studied.ConclusionsOverall our study improves upon the current characterization of CDH1 mutations and their functional role in GC and in individuals at risk of GC. Mutations found in untranslated regions and data on splicing effects deserve a particular attention like associated with a reduced E-cadherin amount. The utility of CDH1 screening, in addition to the identification of other risk factors, could be useful for the early detection of GC in subjects at risk (i.e. FDRs and AMAGs), and warrants further study.

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Effects of Helicobacter pylori Infection on Gastric Parietal Cells and E-cadherin in Mongolian Gerbils

Cited by 7 publications

References 36 publications

Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

Helicobacter suis affects the health and function of porcine gastric parietal cells

Identification and Characterization of CDH1 Germline Variants in Sporadic Gastric Cancer Patients and in Individuals at Risk of Gastric Cancer

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