title: Gastric de novo Muc13 expression and spasmolytic polypeptide-expressing metaplasia during Helicobacter heilmannii infection.
abstract: Helicobacter heilmannii is a zoonotic bacterium that has been associated with gastric disease in humans. In this study, the mRNA expression of mucins in the stomach of BALB/c mice was analyzed at several time points during a 1-year infection with this bacterium, during which gastric disease progressed in severity. Markers for acid production by parietal cells and mucous metaplasia were also examined. In the first 9 weeks postinfection, the mRNA expression of Muc6 was clearly upregulated in both the antrum and fundus of the stomach of H. heilmannii-infected mice. Interestingly, Muc13 was upregulated already at 1 day postinfection in the fundus of the stomach. Its expression level remained high in the stomach over the course of the infection. This mucin is, however, not expressed in a healthy stomach, and high expression of this mucin has so far only been described in gastric cancer. In the later stages of infection, mRNA expression of H(+)/K(+)-ATPase α/β and KCNQ1 decreased, whereas the expression of Muc4, Tff2, Dmbt1, and polymeric immunoglobulin receptor (pIgR) increased starting at 16 weeks postinfection onwards, suggesting the existence of spasmolytic polypeptide-expressing metaplasia in the fundus of the stomach. Mucous metaplasia present in the mucosa surrounding low-grade mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions was also histologically confirmed. Our findings indicate that H. heilmannii infection causes severe gastric pathologies and alterations in the expression pattern of gastric mucins, such as Muc6 and Muc13, as well as disrupting gastric homeostasis by inducing the loss of parietal cells, resulting in the development of mucous metaplasia.
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium Annemieke.Smet@Ugent.be.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Smet
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Blaecher
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Flahou
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Richard
authors.initials: R
authors.lastname: Ducatelle
authors.affiliation: Mucosal Immunobiology and Vaccine Center, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Linden
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Freddy
authors.initials: F
authors.lastname: Haesebrouck
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology*; D018247:Helicobacter heilmannii / Q000254:growth & development*; D036341:Intercellular Signaling Peptides and Proteins; D008679:Metaplasia / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D000071164:Trefoil Factor-2
chemical_list: D000954:Antigens, Surface; D036341:Intercellular Signaling Peptides and Proteins; C063487:Ly64 protein, mouse; D010455:Peptides; C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2; C451060:spasmolytic polypeptide; D004815:Epidermal Growth Factor