Microarray analysis of somatostatin receptor 5-regulated gene expression profiles in murine pancreas.
Microarray analysis of somatostatin receptor 5-regulated gene expression profiles in murine pancreas.
复制标题
小鼠胰腺中生长抑素受体 5 调节基因表达谱的微阵列分析。
DOI：
10.1007/s00268-008-9893-1
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发表时间：
2009
影响因子：
2.6
通讯作者：
Brunicardi,FCharles
中科院分区：
文献类型：
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作者：
Patel,SanjeetG;Zhou,Guisheng;Liu,Shi-He;Li,Min;Jeong,Jae-Wook;DeMayo,FrancescoJ;Gingras,Marie-Claude;Gibbs,RichardA;Fisher,WilliamE;Brunicardi,FCharles
背景我们先前证实生长抑素5型受体（SSTR 5）基因敲除可导致胰岛素分泌和葡萄糖代谢的改变，并伴有胰岛形态学改变。SSTR 5发挥其细胞功能的潜在机制仍然未知。我们假设，SSTR 5介导的生长抑素（SST）对胰岛素分泌和胰岛增殖的抑制作用，通过调节一组特定的胰腺genes.MethodsTo确定SSTR 5调节胰腺基因，基因表达微阵列分析进行了1-和3个月大的野生型（WT）和SSTR 5基因敲除（SSTR 5-/-）雄性小鼠的整个胰腺。Real-time RT-PCR和免疫荧光进行验证选择的差异表达的基因。ResultsA组的143个探针被确定为差异表达在胰腺的1个月大的SSTR 5 −/−小鼠，其中72下调和71上调。在3月龄时，SSTR 5基因切除导致一组30个探针的下调和一组37个探针的上调。在这些差异表达的基因中，分别有15个和5个基因在1月龄和3月龄的小鼠中上调和下调。三个基因，PAP/INGAP，ANG，和TDE 1，被选中进行验证，通过实时RT-PCR和immunofluorescence.ConclusionsA特定的一组基因连接到广泛的细胞功能，如胰岛增殖，凋亡，血管生成和肿瘤的发生是上调或下调在SSTR 5缺陷的雄性小鼠相比，他们在野生型小鼠的表达。因此，这些基因在正常胰腺发育和功能维持过程中是潜在的SSTR 5调控基因。
BackgroundWe 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.MethodsTo identify SSTR5-regulated pancreatic genes, gene expression microarray analysis was performed on the whole pancreas of 1- and 3-month-old wild-type (WT) andSSTR5knockout (SSTR5−/−) male mice. Real-time RT-PCR and immunofluorescence were performed to validate selected differentially expressed genes.ResultsA set of 143 probes were identified to be differentially expressed in the pancreas of 1-month-oldSSTR5−/−mice, 72 of which were downregulated and 71 upregulated. At 3 months of age,SSTR5gene 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, andTDE1, were selected to be validated by real-time RT-PCR and immunofluorescence.ConclusionsA 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 inSSTR5-deficient male mice compared with their expression in wild-type mice. Therefore, these genes are potentialSSTR5-regulated genes during normal pancreatic development and functional maintenance.