Gene expression profiling of gastrin target genes in parietal cells

被引:48
作者
Jain, RN
Brunkan, CS
Chew, CS
Samuelson, LC [1 ]
机构
[1] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
[2] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA USA
关键词
stomach; gastric acid secretion; gene expression microarray; gastrin-deficient mice; fundic mucosa;
D O I
10.1152/physiolgenomics.00133.2005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Previous studies demonstrated that mice with a null mutation in the gene encoding the hormone gastrin have impaired gastric acid secretion. Hence, the aim of this study was to evaluate changes in the acid-secreting parietal cell in gastrin-deficient (GAS-KO) mice. Analysis of several transcripts encoding parietal cell proteins involved in gastric acid secretion showed reduced abundance in the GAS-KO stomach, including H+, K+-ATPase alpha- and beta-subunits, KCNQ1 potassium channel, aquaporin-4 water channel, and creatine kinase B, which were reversed by gastrin infusion for 1 wk. Although mRNA and protein levels of LIM and SH3 domain-containing protein-1 (LASP-1) were not greatly changed in the mutant, there was a marked reduction in phosphorylation, consistent with its proposed role as a cAMP signal adaptor protein associated with acid secretion. A more comprehensive analysis of parietal cell gene expression in GAS-KO mice was performed using the Affymetrix U74AV2 chip with RNA from parietal cells purified by flow cytometry to > 90%. Comparison of gene expression in GAS-KO and wild-type mice identified 47 transcripts that differed by greater than or equal to twofold, suggesting that gastrin affects parietal cell gene expression in a specific manner. The differentially expressed genes included several genes in signaling pathways, with a substantial number (20%) known to be target genes for Wnt and Myc.
引用
收藏
页码:124 / 132
页数:9
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