Microarray analysis of somatostatin receptor 5-regulated gene expression profiles in murine pancreas.

TitleMicroarray analysis of somatostatin receptor 5-regulated gene expression profiles in murine pancreas.
Publication TypeJournal Article
Year of Publication2009
AuthorsPatel, SG, Zhou, G, Liu, S-H, Li, M, Jeong, J-W, DeMayo, FJ, Gingras, M-C, Gibbs, RA, Fisher, WE, F Brunicardi, C
JournalWorld J Surg
Volume33
Issue4
Pagination630-7
Date Published2009 Apr
ISSN0364-2313
KeywordsAnimals, Apoptosis, Cell Proliferation, Down-Regulation, Fluorescent Antibody Technique, Gene Expression Profiling, Islets of Langerhans, Male, Mice, Mice, Knockout, Neoplasm Proteins, Neovascularization, Pathologic, Oligonucleotide Array Sequence Analysis, Pancreas, Pancreatitis-Associated Proteins, Proteins, Receptors, Cell Surface, Receptors, Somatostatin, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease, Pancreatic, Up-Regulation
Abstract

BACKGROUND: We previously demonstrated that somatostatin receptor type 5 (SSTR5) gene ablation results in alterations in insulin secretion and glucose metabolism, accompanied by morphologic alterations in the islets of Langerhans. The underlying mechanism(s) by which SSTR5 exerts its cellular functions remain(s) unknown. We hypothesized that SSTR5 mediates the inhibitory effect of somatostatin (SST) on insulin secretion and islet proliferation by regulating a specific set of pancreatic genes.METHODS: To identify SSTR5-regulated pancreatic genes, gene expression microarray analysis was performed on the whole pancreas of 1- and 3-month-old wild-type (WT) and SSTR5 knockout (SSTR5-/-) male mice. Real-time RT-PCR and immunofluorescence were performed to validate selected differentially expressed genes.RESULTS: A set of 143 probes were identified to be differentially expressed in the pancreas of 1-month-old SSTR5-/- mice, 72 of which were downregulated and 71 upregulated. At 3 months of age, SSTR5 gene ablation resulted in downregulation of a set of 30 probes and upregulation of a set of 37 probes. Among these differentially expressed genes, there were 15 and 5 genes that were upregulated and downregulated, respectively, in mice at both 1 and 3 months of age. Three genes, PAP/INGAP, ANG, and TDE1, were selected to be validated by real-time RT-PCR and immunofluorescence.CONCLUSIONS: A specific set of genes linked to a wide range of cellular functions such as islet proliferation, apoptosis, angiogenesis, and tumorigenesis were either upregulated or downregulated in SSTR5-deficient male mice compared with their expression in wild-type mice. Therefore, these genes are potential SSTR5-regulated genes during normal pancreatic development and functional maintenance.

DOI10.1007/s00268-008-9893-1
Alternate JournalWorld J Surg
PubMed ID19137362
Grant ListR01-DK46441 / DK / NIDDK NIH HHS / United States
R13 CA132572 / CA / NCI NIH HHS / United States