Loss of parietal cell expression of Sonic hedgehog induces hypergastrinemia and hyperproliferation of surface mucous cells.
Loss of parietal cell expression of Sonic hedgehog induces hypergastrinemia and hyperproliferation of surface mucous cells.
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DOI：
10.1053/j.gastro.2009.11.002
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发表时间：
2010-02
期刊：
影响因子：
29.4
通讯作者：
Zavros Y
中科院分区：
文献类型：
--
作者：
Xiao C;Ogle SA;Schumacher MA;Orr-Asman MA;Miller ML;Lertkowit N;Varro A;Hollande F;Zavros Y
Sonic Hedgehog (Shh) 在成人胃中表达，但其作为胃形态发生素的作用尚不清楚。我们试图确定 Shh 调节胃上皮细胞功能和分化的机制。创建了具有壁细胞特异性 Shh 缺失的小鼠 (HKCre/ShhKO)。研究人员对 1 至 8 个月大的对照小鼠和 HKCre/ShhKO 小鼠的胃形态和功能进行了研究。与对照小鼠相比，HKCre/ShhKO 小鼠出现胃酸过少、高胃泌素血症和类似于中心凹增生的表型。 HKCre/ShhKO 小鼠的胃底粘膜具有扩大的表面凹陷细胞谱系，这通过溴脱氧尿苷掺入的增加来记录，并归因于高胃泌素血症。与对照组相比，HKCre/ShhKO 小鼠胃中总粘液颈细胞和酶原细胞数量显着减少。此外，酶原和颈部细胞标记物在相同的细胞群中共表达，表明 HKCre/ShhKO 小鼠胃中的粘液颈部细胞的酶原细胞谱系的分化被破坏。对表面上皮进行激光捕获显微切割，然后进行定量逆转录聚合酶链反应，结果显示 Indian Hedgehog、神经胶质瘤相关癌基因同源物 1、Wnt 和细胞周期蛋白 D1 的表达显着增加。激光捕获显微切割分析还显示，Snail 显着增加，同时 E-钙粘蛋白减少。在成年小鼠的胃中，壁细胞失去 Shh 会导致胃酸过少和高胃泌素血症。高胃泌素血症可能随后诱导表面小凹上皮中 Hedgehog 和 Wnt 信号传导增加，导致过度增殖。
Sonic Hedgehog (Shh) is expressed in the adult stomach, but its role as a gastric morphogen is unclear. We sought to identify mechanisms by which Shh might regulate gastric epithelial cell function and differentiation. Mice with a parietal cell–specific deletion of Shh (HKCre/ShhKO) were created. Gastric morphology and function were studied in control and HKCre/ShhKO mice between 1 and 8 months of age. In contrast to control mice, HKCre/ShhKO mice developed gastric hypochlorhydria, hypergastrinemia, and a phenotype that resembled foveolar hyperplasia. The fundic mucosa of HKCre/ShhKO mice had an expanded surface pit cell lineage that was documented by increased incorporation of bromodeoxyuridine and was attributed to the hypergastrinemia. Compared with controls, numbers of total mucous neck and zymogen cells were significantly decreased in stomachs of HKCre/ShhKO mice. In addition, zymogen and neck cell markers were coexpressed in the same cell populations, indicating disrupted differentiation of the zymogen cell lineage from the mucous neck cells in the stomachs of HKCre/ShhKO mice. Laser capture microdissection of the surface epithelium, followed by quantitative reverse-transcription polymerase chain reaction, revealed a significant increase in expression of Indian Hedgehog, glioma-associated oncogene homolog 1, Wnt, and cyclin D1. Laser capture microdissection analysis also showed a significant increase in Snail with a concomitant decrease in E-cadherin. In the stomachs of adult mice, loss of Shh from parietal cells results in hypochlorhydria and hypergastrinemia. Hypergastrinemia might subsequently induce increased Hedgehog and Wnt signaling in the surface pit epithelium, resulting in hyperproliferation.
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影响因子：
2.7
作者：
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