INS-1-3细胞内质网应激伴随 MODY基因通路表达的变化

Endoplasmic reticulum stress in INS-1-3 cell associated with the expression changes of MODY gene ;pathway

目的：研究INS-1-3细胞（大鼠胰岛素高分泌细胞亚系）经毒胡萝卜素和衣霉素处理后造成内质网应激的基因表达谱变化。方法以正常培养的INS-1-3细胞为对照组，通过毒胡萝卜素（ TG组，0.1μmol／L，16 h）和衣霉素（ TM组，2.5μg／ml，16 h）建立内质网应激模型，收集样本进行数字基因表达谱分析，筛选差异表达基因并进行差异基因表达模式聚类分析，基因本体论（ GO）功能和pathway富集分析，并通过定量PCR对部分差异表达基因进行验证。结果 TG组和TM组分别与对照组比较，筛选出的差异基因数目分别为57个（其中上调基因45个，下调基因12个）和135个（其中上调基因99个，下调基因36个）。 GO功能显著性富集分析显示，细胞组分主要富集在内质网区域。pathway富集分析显示，共同显著富集的途径包括内质网应激、抗原的加工与提呈、蛋白运输和青少年发病的成人型糖尿病（MODY）通路。结论内质网应激的情况下，MODY信号通路相关转录因子表达发生变化可能与胰岛β细胞功能发生改变有关。

Objective To profile the gene expression changes associated with endoplasmic reticulum stress in INS-1-3 cells induced by thapsigargin （TG） and tunicamycin （TM）.Methods Normal cultured INS-1-3 cells were used as a control.TG and TM were used to induce endoplasmic reticulum stress in INS-1-3 cells.Digital gene expression profiling technique was used to detect differentially expressed gene .The changes of gene expression were detected by expression pattern clustering analysis , gene ontology （ GO） function and pathway enrichment analysis.Real time polymerase chain reaction （ RT-PCR ） was used to verify the key changes of gene expression.Results Compared with the control group , there were 57 （ 45 up-regulated, 12 down-regulated） and 135 （99 up-regulated, 36 down-regulated） differentially expressed genes in TG and TM group , respectively.GO function enrichment analyses indicated that the main enrichment was in the endoplasmic reticulum.In signaling pathway analysis , the identified pathways were related with endoplasmic reticulum stress , antigen processing and presentation , protein export , and most of all, the maturity onset diabetes of the young （ MODY ） pathway.Conclusion Under the condition of endoplasmic reticulum stress , the related expression changes of transcriptional factors in MODY signaling pathway may be related with the impaired function in islet beta cells.