西格列汀对NOD小鼠甲状腺基因表达的影响

Effect of sitagliptin on gene expression of thyroid in NOD mice

目的筛选二肽基肽酶4 (DPP-4)抑制剂和安慰剂干预NOD小鼠的甲状腺组织中差异表达基因(DEGs)和通路,探讨DPP-4抑制剂对NOD小鼠甲状腺基因表达的影响及可能的信号通路。方法将DPP-4抑制剂和安慰剂干预的NOD小鼠的甲状腺组织进行分离纯化。通过基因芯片技术筛选分析获得DEGs,并进行GO (Gene Ontology)功能分析及京都基因与基因组百科全书(KEGG)通路富集分析。结果根据基因芯片的数据结果进行分析,与对照组相比,基因芯片筛选出NOD小鼠甲状腺组织中DEGs 475个,其中表达上调290个,表达下调185个。GO功能分析显示DEGs主要参与生物学功能如皮肤屏障及T细胞分化及分子功能如泛素结合酶活性,此外还与突触后调节相关。KEGG通路分析显示DEGs富集于花生四烯酸代谢通路、炎症性肠病及代谢通路。miR-568是表达上调最显著的基因,而miR-686是表达下调最显著的基因。结论 DPP-4抑制剂对NOD小鼠甲状腺组织花生四烯酸代谢等多个信号通路存在影响,可能对1型糖尿病患者的甲状腺自身免疫功能存在影响。

【Objective】 To screen the differentially expressed genes(DEGs) and signaling pathway in the thyroid of non-obese diabetes(NOD) mice treated with dipeptidyl peptidase-4(DPP-4) inhibitor or saline and explore the effect of DPP-4 inhibitor on the gene expression and signaling pathway in NOD mice.【Methods】 The thyroids of NOD mice treated with DPP-4 inhibitor or saline were isolated and purified.Gene microarray analysis was conducted to identified DEGs,followed with Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis.【Results】 A total of 475 DEGs were identified,among which,290 genes were up-regulated and 185 genes were down-regulated.According to GO function analysis,DEGs were mainly involved in biological process such as establishment of skin barrier and T-helper cell differentiation;molecular function such as ubiquitin conjugating enzyme activity and regulated cellular component such as postsynapse.According to KEGG pathway analysis,DEGs were mainly enriched in arachidonic acid metabolism,inflammatory bowel disease and metabolic pathways.miRNA-568 was identified as the most up-regulated gene,while miRNA-686 as the most down-regulated gene.【Conclusion】 DPP-4 inhibitor has effect on multiple signaling pathway(eg.arachidonic acid metabolism) in the thyroid of NOD mice,which suggests it has effect on autoimmunity of thyroid in type 1 diabetes.