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01.12.2010 | Original Article

Acid Suppression by Proton Pump Inhibitors Enhances Aquaporin-4 and KCNQ1 Expression in Gastric Fundic Parietal Cells in Mouse

verfasst von: Juntaro Matsuzaki, Hidekazu Suzuki, Yuriko Minegishi, Etsuko Sugai, Hitoshi Tsugawa, Masato Yasui, Toshifumi Hibi

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2010

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Abstract

Background

The widespread use of proton pump inhibitors (PPIs) is known to cause sporadic gastric fundic gland polyps (FGPs). Altered expression and localization of the water or ion transport proteins might contribute to the excess fluid secretion into the cystic lumen for the development of FGPs.

Aims

We investigated the alteration of the murine gastric fundic mucosa after PPI treatment, and examined the expression of water channel aquaporin-4 (AQP4) and potassium channel KCNQ1, which are expressed only in the parietal cells in the gastric mucosa.

Methods

Male 5-week-old C57BL/6J mice were administered lansoprazole (LPZ) by subcutaneous injection for 8 weeks. The expression of AQP4 and KCNQ1 were investigated by Western blotting, quantitative RT-PCR, and immunohistochemistry. The expression of mucin-6 (Muc6), pepsinogen, and sonic hedgehog (Shh) were also investigated as mucosal cell lineage markers.

Results

Gastric mucosal hyperplasia with multiple cystic dilatations, exhibiting similar histological findings to the FGPs, was observed in the LPZ-treated mice. An increase in the number of AQP4-positive parietal cells and KCNQ1-positive parietal cells was observed. The extension of the distribution of AQP4-positive cells toward the surface of the fundic glands was also observed. The expression levels of AQP4 mRNA and protein were significantly enhanced. The expression of KCNQ1 mRNA was correlated with that of AQP4 mRNA in the LPZ-treated mice. Mucous neck-to-zymogenic cell lineage differentiation was delayed in association with decreased expression of Shh in the LPZ-treated mice.

Conclusions

PPI administration increased the number of parietal cells with enhanced expression of AQP4 and KCNQ1.

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Titel: Acid Suppression by Proton Pump Inhibitors Enhances Aquaporin-4 and KCNQ1 Expression in Gastric Fundic Parietal Cells in Mouse
verfasst von: Juntaro Matsuzaki
Hidekazu Suzuki
Yuriko Minegishi
Etsuko Sugai
Hitoshi Tsugawa
Masato Yasui
Toshifumi Hibi
Publikationsdatum: 01.12.2010
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 12/2010
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-010-1167-8

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Acid Suppression by Proton Pump Inhibitors Enhances Aquaporin-4 and KCNQ1 Expression in Gastric Fundic Parietal Cells in Mouse

Abstract

Background

Aims

Methods

Results

Conclusions

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Abstract

Background

Aims

Methods

Results

Conclusions

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