Gene expression profiling of gastrin target genes in parietal cells.
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.
Jain
Renu N
RN
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109-0622, USA.
Brunkan
Cynthia S
CS
Chew
Catherine S
CS
Samuelson
Linda C
LC
D000818:Animals; D003598:Cytoskeletal Proteins; D005434:Flow Cytometry; D005744:Gastric Acid / Q000378:metabolism; D005748:Gastric Fundus / Q000166:cytology; D005755:Gastrins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D060588:LIM Domain Proteins; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003598:Cytoskeletal Proteins; D005755:Gastrins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C490692:Lasp1 protein, mouse; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D017506:H(+)-K(+)-Exchanging ATPase