Along with the histological findings, the

mRNA expression level of AQP4 in the stomach of the H2R knockout mouse was significantly higher than that of wild type regardless of the aging period (Fig. 2a). However, the mRNA expression level of AQP4 in 60 weeks old was significantly lower than those in 20 weeks old. The mRNA expression level of H+/K+-ATPase in the stomach of the H2R knockout mouse was higher than that of wild type at the age of 20 weeks and 40 weeks (Fig. 2b). However, it was gradually decreased through the aging in the H2R knockout mouse. In addition, the ratio HDAC activation of the mRNA expression between AQP4 and H+/K+-ATPase were higher in the H2R knockout mouse regardless of the aging period compared with wild type (Fig. 2c). To summarize these data, the mucosal hyperplasia was induced in the H2R knockout mouse and was aggravated by aging along with the decrease of the mRNA expression of H+/K+-ATPase. The mRNA expression of AQP4 was significantly higher in the H2R knockout mouse but was decreased by aging. The higher ratio of mRNA expression between AQP4 and H+/K+-ATPase was kept

in the H2R knockout mouse, suggesting that the decrease of AQP4 mRNA levels by aging was caused by reduced viability of gastric parietal cells. Subsequently, the influence on H. pylori infection for the gastric mucosal status of SPEM was assessed in wild type or the H2R knockout mice. In the wild type mice, the mRNA expression level of Shh, which is a morphogen for differentiation of gastric mucosal cells, in the stomach was significantly decreased by H. pylori infection (Fig. 3a). Nutlin-3 molecular weight In the H2R knockout mouse, the mRNA expression level of Shh

was lower than that of wild type. The mRNA expression this website level of Shh was the lowest in the H2R knockout mouse with H. pylori infection. The mRNA level of TFF2, which is an indicator of SPEM, was significantly higher in the H2R knockout mouse compared with that of wild type (Fig. 3b). Furthermore, it was increased by H. pylori infection in the wild type and in the H2R knockout mouse. These data suggest that SPEM in the H2R knockout mouse with H. pylori infection would be the most severe among these mice. The fluorescent immunochemistry of AQP4 and H+/K+-ATPase was performed using these mice. In the wild type mice, the infection of H. pylori decreased the expression of AQP4 in the stomach (Fig. 4). Similarly, in the H2R knockout mouse, the infection of H. pylori suppressed the expression of AQP4 as compared with that without the infection of H. pylori, while mucosal hyperplasia with multiple cystic dilatations was observed regardless of the infection of H. pylori. The mRNA expression of AQP4 was significantly decreased by infection of H. pylori in the wild type as well as in the H2R knockout mouse (Fig. 5a). The mRNA expression level of H+/K+-ATPase was also decreased by infection of H.