title: Mucosal expression of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori-infected mice.
abstract: OBJECTIVE
  Basolateral water channel, aquaporin-4 (AQP4), is known to be expressed in gastric parietal cells, especially in the basal side of gastric mucosa. However, the role of AQP4 in the stomach is still unknown. Histamine type 2 receptor (H2R) knockout mice, which are characterized by suppressed gastric acid secretion, are known as formation of mucosal hyperplasia with cystic dilatation and spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. The aim of the present study is to investigate whether the expression of AQP4 is changed by the condition of acid suppression and Helicobacter pylori infection.
  
  
  METHODS
  Male H2 R knockout mice and their controls (C57BL/6) were used. H. pylori was orally infected at the age of 5 weeks. The distributions of AQP4 and H+/K+-ATPase in the gastric mucosa were investigated by fluorescent immunohistochemistry. The mRNA expressions of AQP4, H+/K+-ATPase, sonic hedgehog (Shh), and trefoil factor-2 (TFF2) were investigated by quantitative reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  In the H2 R knockout mice, the distribution of AQP4-positive parietal cells was extended toward the surface of the fundic glands. Although the mRNA expression levels of AQP4 and H+/K+ATPase were elevated in H2 R knockout mice at the age of 20 weeks, the elevations were not maintained by aging or H. pylori infection. In H2 R knockout mice with H. pylori infection, the expression level of TFF2 mRNA was elevated while the ratio between AQP4 and H+/K+ ATPase mRNA expression was decreased compared with the H2 R knockout mice without H. pylori infection.
  
  
  CONCLUSIONS
  In the H2 R knockout mice, massive SPEM was induced by H. pylori colonization and the ratio between AQP4 and H+/K+ATPase mRNA expression was decreased.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Juntaro
authors.initials: J
authors.lastname: Matsuzaki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsugawa
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Masaoka
authors.forename: Sawako
authors.initials: S
authors.lastname: Miyoshi
authors.forename: Hideki
authors.initials: H
authors.lastname: Mori
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Masato
authors.initials: M
authors.lastname: Yasui
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics* / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology*; D005756:Gastritis / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology*; D015870:Gene Expression; D055786:Gene Knockout Techniques; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D016481:Helicobacter Infections; D016480:Helicobacter pylori; D006965:Hyperplasia; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008679:Metaplasia; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011968:Receptors, Histamine / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071164:Trefoil Factor-2
chemical_list: D051401:Aquaporin 4; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D012333:RNA, Messenger; D011968:Receptors, Histamine; C465570:Shh protein, mouse; C481546:TFF2 protein, mouse; D000071164:Trefoil Factor-2; C451060:spasmolytic polypeptide; D017506:H(+)-K(+)-Exchanging ATPase
keywords: Helicobacter pylori; SPEM; acid suppression; aquaporin-4