Transcriptional profiling of gastrin-regulated genes in mouse stomach.
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.
Jain
Renu N
RN
Department of Molecular and Integrative Physiology, The University of Michigan, Ann Arbor, Michigan 48109-2200, USA.
Samuelson
Linda C
LC
D000818:Animals; D002766:Cholecystokinin / Q000235:genetics; D019861:Enterochromaffin-like Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000166:cytology*
D005755:Gastrins; D002766:Cholecystokinin