Gastric body mucosa atrophy predisposes one to gastric cancer. Disturbances in the gastric differentiation process might play a role in the evolution of gastric atrophy. Sonic hedgehog (Shh) has recently been implicated as a crucial factor in gastric organogenesis and gland differentiation. In this study we investigated the expression of key factors in the Shh pathway, namely Shh and its receptor Patched (Ptc), in normal and pathologic stomach mucosa. Furthermore, the potential role of pH for Shh dysregulation was analyzed. Ten gastric biopsy specimens each from normal gastric mucosa, chronic nonatrophic gastritis, atrophic gastritis, and gastric cancer were included. Expression of Shh and Ptc was analyzed by immunohistochemistry. In normal body mucosa and in nonatrophic body gastritis, Shh was strongly expressed in parietal cells. Ptc was also expressed in gastric chief cells. Shh expression was almost completely lost in atrophic gastritis and in gastric cancer and absent in intestinal metaplasia. Ptc was markedly reduced in atrophy and only weakly positive in intestinal metaplasia and gastric cancer. In in vitro experiments, gastric cancer cell line 23132 was found positive for Shh. In long-term culture as well as in culture conditions with low pH, transcription of Shh in 23132 was significantly increased in quantitative reverse transcription PCR analyses. We concluded that the decreased expression of the Shh pathway in atrophic gastritis and gastric cancer might reflect altered differentiation processes within the gastric unit and contributes to the development of gastric atrophy. The increase of gastric pH might play a role in the development of gastric mucosa atrophy via reduction of Shh transcription.

中文翻译：

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sonic hedgehog 的转录是胃形态发生和胃粘膜维持的潜在因子，在酸性条件下上调。

胃体粘膜萎缩易患胃癌。胃分化过程中的紊乱可能在胃萎缩的演变中起作用。声波刺猬 (Shh) 最近被认为是胃器官发生和腺体分化的关键因素。在这项研究中，我们研究了 Shh 通路中关键因子的表达，即 Shh 及其受体 Patched (Ptc)，在正常和病理胃粘膜中的表达。此外，还分析了 pH 对 Shh 失调的潜在作用。包括来自正常胃粘膜、慢性非萎缩性胃炎、萎缩性胃炎和胃癌的十个胃活检标本。通过免疫组织化学分析 Shh 和 Ptc 的表达。在正常体粘膜和非萎缩性体胃炎中，Shh 在壁细胞中强烈表达。Ptc 也在胃主细胞中表达。Shh 表达在萎缩性胃炎和胃癌中几乎完全丧失，在肠化生中不存在。Ptc在萎缩中显着降低，在肠化生和胃癌中仅呈弱阳性。在体外实验中，发现胃癌细胞系 23132 对 Shh 呈阳性。在长期培养和低 pH 培养条件下，23132 中 Shh 的转录在定量逆转录 PCR 分析中显着增加。我们得出结论，Shh 通路在萎缩性胃炎和胃癌中的表达降低可能反映了胃单元内分化过程的改变，并促进了胃萎缩的发展。