Sonic hedgehog in gastric physiology and neoplastic transformation: friend or foe?
Sonic hedgehog in gastric physiology and neoplastic transformation: friend or foe?
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DOI：
10.1097/med.0b013e328320a821
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Merchant JL
中科院分区：
文献类型：
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作者：
El-Zaatari M;Saqui-Salces M;Waghray M;Todisco A;Merchant JL
了解音刺猬蛋白（Shh）在正常胃生理和肿瘤转化中的作用。新出现的证据表明，胃上皮细胞产生Shh配体，其随后靶向间充质。这种旁分泌信号事件被Shh产生肿瘤重演，其向支持基质发出信号以促进生长。初级纤毛含有刺猬（Hh）信号装置的组件，因此通常在响应基质细胞上发现。在胃中，Shh在上皮细胞中产生并由间充质中的响应细胞接收。在体外，Shh增强胃酸分泌并诱导粘蛋白表达。它仍然有待确定是否典型的信号通路介导观察到的上皮细胞的影响。Shh表达和信号在慢性胃炎中减少，Shh-/-胚胎在胃粘膜中表现出增生和化生变化。在其在胃体中丢失后，Shh在通常在远端胃或胃窦中产生的一些胃癌中重新表达，这表明Shh促进肿瘤生长。
To understand the role of sonic hedgehog (Shh) in normal gastric physiology and neoplastic transformation. Emerging evidence shows that gastric epithelial cells produce Shh ligand, which subsequently targets the mesenchyme. This paracrine signaling event is recapitulated by Shh-producing tumors that signal to the supporting stroma to encourage growth. Primary cilia contain components of the hedgehog (Hh) signaling apparatus, and thus are typically found on responding stromal cells. In the stomach, Shh is produced in epithelial cells and received by responding cells in the mesenchyme. In vitro, Shh enhances gastric acid secretion and induces mucin expression. It remains to be determined whether the canonical signaling pathway mediates the observed epithelial effects. Shh expression and signaling is reduced in chronic gastritis, and Shh−/− embryos exhibit hyperplasia and metaplastic changes in the gastric mucosa. After its loss in the corpus, Shh is re-expressed in some gastric carcinomas typically arising in the distal stomach or antrum suggesting that Shh promotes tumor growth.