Basic ResearchGenetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice☆,**,★
Section snippets
Animals
G−/− (n = 12) mice and strain-matched (129/Sv) wild-type controls (gastrin-expressing [G+/+], n = 12) were bred by homozygous mating. Mice were kept in individual, sterile, microisolator cages in nonbarrier mouse rooms for 16 weeks (conventional housing). Food and water were not autoclaved. No additional procedures were used to house the mice in rooms separate from those that have been intentionally infected with other bacterial pathogens. All mice were fasted overnight with access to water ad
Mucosal inflammation in G−/− mice
The effect of hypochlorhydria on gastric pathology in the G−/− mice was evaluated. Sixteen-week-old G−/− mice showed mucosal thickening and significant inflammation (Figure 1B) compared with the G+/+ mice (Figure 1A).
Discussion
The findings reported here show that a major consequence of hypochlorhydria induced genetically or chemically is the generation of an inflammatory response. In G−/− mice, lymphocytes were elevated above levels measured in the wild-type (G+/+) animals. Similarly, wild-type mice treated with omeprazole had increased numbers of lymphocytes, indicative of chronic inflammation. This result is consistent with prior studies showing that humans treated with omeprazole also become colonized with gastric
Acknowledgements
The authors thank the flow cytometry core in the University of Michigan Cancer Center (CA46952) and University of Michigan Multipurpose Arthritic Center (AR20557), and the assistance of the radioligand core of the University of Michigan Gastrointestinal Peptide Research Center (DK-34533) for their technical assistance. They also acknowledge the use of rabbit gastrin antibody #1296 from CURE DDRC/RIA Core (DK41301). The authors thank Chris Dickinson for synthesizing iodinated gastrin peptide,
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2020, Cell Stem CellCitation Excerpt :We show here that gastrin deficiency or carcinogen exposure leads to increased symmetric cell division, accumulation of mutations, and cancer progression. While hypergastrinemia promotes gastric corpus proliferation and tumorigenesis (Hayakawa et al., 2016), gastrin deficiency has been linked to antral tumor development (Zavros et al., 2002). We have shown that gastrin-deficient mice are more susceptible to MNU-induced antral tumorigenesis and that elevations in amidated gastrin suppressed antral tumorigenesis in a manner that correlated with gene silencing and epigenetic alterations of Tff1 (Takaishi et al., 2009; Tomita et al., 2011).
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2016, Current Opinion in PharmacologyCitation Excerpt :Similarly, in studies on Mongolian gerbils infected with H. pylori, long-term PPI administration promotes the progression of atrophic corpus gastritis and cancer [26]. However, reports emerged soon thereafter that gastrin knockout (GAS-KO) mice also developed tumors of the stomach, often spontaneously [27–29]. GAS-KO mice showed hypochlorhydria and bacterial overgrowth, and tumor development was promoted by conventional housing, suggesting the role of abnormal bacterial colonization and subsequent inflammation induced by hypochrorhydria.
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Address requests for reprints to: Juanita L. Merchant, M.D., Ph.D., 1150 West Medical Drive, MSRB I, 3510, Ann Arbor, Michigan 48109-0650. e-mail: [email protected]; fax: (734) 936-1400.
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Supported in part by Public Health Service grant DK-45729 (to J.L.M.) and DK48815 (to L.C.S.).
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Y.Z. is an associate and J.L.M. is an assistant investigator of the Howard Hughes Medical Institute.