Transcriptional profiling of gastrin-regulated genes in mouse stomach
Transcriptional profiling of gastrin-regulated genes in mouse stomach
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DOI：
10.1152/physiolgenomics.00176.2006
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发表时间：
2007-03-14
影响因子：
4.6
通讯作者：
Samuelson, Linda C.
中科院分区：
文献类型：
--
作者：
Jain, Renu N.;Samuelson, Linda C.
胃泌素是一种有效的胃酸分泌刺激剂，主要靶向胃中分泌酸的壁细胞和分泌组胺的肠嗜铬样（ECL）细胞。因此，胃泌素缺乏（GAS-KO）小鼠在酸分泌方面具有严重的损害。本研究的目的是表征GAS-KO小鼠基因表达的变化，以确定胃泌素调节的基因，并深入了解胃细胞类型如何受胃泌素和酸分泌的调节。GAS-KO和野生型小鼠的亲和微阵列分析鉴定了许多差异表达的转录物。将结果与用胃泌素处理的GAS-KO小鼠进行比较，以鉴定胃泌素应答的基因。最后，通过与缺乏胃泌素和胆囊收缩素（GAS/CCK-KO）的小鼠进行比较，鉴定了主要由于胃泌素而不是低氯血症而改变的基因，因为这些小鼠已经恢复了基础酸分泌。通过定量逆转录聚合酶链反应分析验证数据。有趣的是，许多炎症反应基因在GAS-KO小鼠中被诱导，并在GAS/CCK-KO小鼠中正常化，这表明它们在对低胃酸的反应中增加。此外，在GAS-KO小鼠中下调的许多壁细胞转录物在GAS/CCK-KO小鼠中类似地恢复，表明壁细胞变化也主要与低氯血症相关。相反，在GAS-KO小鼠中显著下调的ECL细胞基因在GAS/CCK-KO小鼠中继续减少，表明胃泌素协调调节许多ECL细胞基因，包括参与组胺合成和分泌的几个基因。
Gastrin, a potent stimulator of gastric acid secretion, primarily targets the acid-secreting parietal cells and histamine-secreting enterochromaffin-like (ECL) cells in the stomach. Accordingly, gastrin-deficient (GAS-KO) mice have a severe impairment in acid secretion. The aim of this study was to characterize changes in gene expression in GAS-KO mice to identify gastrin-regulated genes and to gain insight into how gastric cell types are regulated by gastrin and acid secretion. Affymetrix microarray analysis of GAS-KO and wild-type mice identified numerous differentially expressed transcripts. The results were compared with GAS-KO mice treated with gastrin to identify genes that were gastrin responsive. Finally, genes that were primarily changed due to gastrin and not hypochlorhydria were identified by comparison to mice that are deficient in both gastrin and cholecystokinin (GAS/CCK-KO), since these mice have restored basal acid secretion. The data were validated by quantitative reverse transcriptase polymerase chain reaction analysis. Interestingly, a number of inflammatory response genes were induced in GAS-KO mice and normalized in GAS/CCK-KO mice, suggesting that they were increased in response to low gastric acid. Moreover, a number of parietal cell transcripts that were downregulated in GAS-KO mice were similarly restored in GAS/CCK-KO mice, suggesting that parietal cell changes were also primarily associated with hypochlorhydria. In contrast, ECL cell genes that were markedly downregulated in GAS-KO mice continued to be reduced in GAS/CCK-KO mice, demonstrating that gastrin coordinately regulates a number of ECL cell genes, including several involved in histamine synthesis and secretion.