Mucosal expression of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori-infected mice

Seiichiro Fukuhara, Juntaro Matsuzaki, Hitoshi Tsugawa, Tatsuhiro Masaoka, Sawako Miyoshi, Hideki Mori, Yasushi Fukushima, Masato Yasui, Takanori Kanai, Hidekazu Suzuki
Journal of Gastroenterology and Hepatology 2014, 29 Suppl 4: 53-9

BACKGROUND AND AIM: 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.

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