Intracellular calcium release and protein kinase C activation stimulate sonic hedgehog gene expression during gastric acid secretion.
Intracellular calcium release and protein kinase C activation stimulate sonic hedgehog gene expression during gastric acid secretion.
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DOI：
10.1053/j.gastro.2010.08.047
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发表时间：
2010-12
期刊：
影响因子：
29.4
通讯作者：
Merchant JL
中科院分区：
文献类型：
--
作者：
El-Zaatari M;Zavros Y;Tessier A;Waghray M;Lentz S;Gumucio D;Todisco A;Merchant JL
幽门螺杆菌感染期间的低氯血症抑制胃Shh表达。我们研究了酸分泌机制是否通过Ca 2+依赖性蛋白激酶C（PKC）或cAMP依赖性蛋白激酶A（PKA）激活来调节Shh基因的表达。我们通过转基因过表达刺猬相互作用蛋白-1（sHip-1）的分泌形式阻断了刺猬信号传导，sHip-1是一种天然的刺猬配体抑制剂，可诱导低氯血症。钆、EGTA+BAPTA、PKC过表达腺病毒和PKC抑制剂用于调节原代胃细胞、器官和AGS细胞系培养物中的Ca 2 + i释放、PKC活性和Shh基因表达。在H+/K+-β-霍乱毒素过表达小鼠（Ctox）中诱导PKA过度活性。表达sHip-1的小鼠胃酸水平较低（hypochlorobenzia），生长抑素的产生减少，胃泌素基因表达增加。这些小鼠中的次氯酸盐抑制Shh基因表达，与奥美拉唑治疗野生型小鼠获得的水平相似。然而，Shh的表达也被抑制在高盐酸Ctox模型与升高的cAMP，这表明调节Shh不仅是酸依赖性的，但涉及到特定的酸刺激信号通路。基于以前的报道，Ca 2 + i释放也刺激壁细胞中的酸分泌，我们发现钆，毒胡萝卜素和卡巴胆碱介导的Ca 2 +i释放诱导Shh表达。Ca 2+螯合BAPTA+EGTA减少Shh的表达。Shh基因表达受PKC-α、-β和-δ（而非PKC-ε）的诱导。此外，佛波酯诱导Shh调节的报告基因。刺激胃酸分泌的促分泌素通过增加Ca 2 + i释放和PKC激活诱导Shh基因表达。Shh可能是通过调节G细胞分泌胃泌素来调节胃酸的配体。
Hypochlorhydria during Helicobacter pylori infection inhibits gastric Shh expression. We investigated whether acid-secretory mechanisms regulate Shh gene expression through Ca2+i-dependent protein kinase C (PKC) or cAMP-dependent protein kinase A (PKA)-activation. We blocked Hedgehog signaling by transgenically overexpressing a secreted form of the Hedgehog interacting protein-1 (sHip-1), a natural inhibitor of hedgehog ligands, which induced hypochlorhydria. Gadolinium, EGTA+BAPTA, PKC-overexpressing adenoviruses, and PKC-inhibitors were used to modulate Ca2+i-release, PKC-activity and Shh gene expression in primary gastric cell, organ, and AGS cell line cultures. PKA hyperactivity was induced in the H+/K+-β-cholera-toxin overexpressing mice (Ctox). Mice that expressed sHip-1 had lower levels of gastric acid (hypochlorhydria), reduced production of somatostatin, and increased gastrin gene expression. Hypochlorhydria in these mice repressed Shh gene expression, similar to the levels obtained with omeprazole treatment of wild-type mice. However, Shh expression was also repressed in the hyperchlorhydric Ctox model with elevated cAMP, suggesting that the regulation of Shh was not solely acid-dependent, but pertained to specific acid-stimulatory signaling pathways. Based on previous reports that Ca2+i-release also stimulates acid secretion in parietal cells, we showed that gadolinium-, thapsigargin- and carbachol-mediated release of Ca2+i induced Shh expression. Ca2+-chelation with BAPTA+EGTA reduced Shh expression. Overexpression of PKC-α, -β and -δ (but not PKC-ε) induced Shh gene expression. In addition, phorbol esters induced a Shh-regulated reporter gene. Secretagogues that stimulate gastric acid secretion induce Shh gene expression through increased Ca2+i-release and PKC activation. Shh might be the ligand transducing changes in gastric acidity to the regulation of G-cell secretion of gastrin.
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DOI：
10.1097/med.0b013e328320a821
发表时间：
2009-02
期刊：
Current opinion in endocrinology, diabetes, and obesity
影响因子：
--
作者：
El-Zaatari M;Saqui-Salces M;Waghray M;Todisco A;Merchant JL
通讯作者：
Merchant JL
DOI：
10.1152/ajpgi.00461.2005
发表时间：
2006-05-01
影响因子：
4.5
作者：
Lopez-Diaz, L;Hinkle, KL;Samuelson, LC
通讯作者：
Samuelson, LC
影响因子：
7.3
作者：
Suzuki, H;Minegishi, Y;Hibi, T
通讯作者：
Hibi, T
DOI：
10.1152/ajpgi.1997.272.2.g246
发表时间：
1997-02-01
影响因子：
4.5
作者：
Chew, CS;Zhou, CJ;Parente, JA
通讯作者：
Parente, JA
影响因子：
5.2
作者：
Heo, Jung Sun;Lee, Min Young;Han, Ho Jae
通讯作者：
Han, Ho Jae