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高糖环境对胰岛β细胞系转录组表达谱的影响
Effect of high glucose environment on transcriptome expression profile of islet β cell line
- 第三军医大学学报 2021年43卷第7期 页码：584-592
- 作者机构：
1.400038 重庆，陆军军医大学（第三军医大学）：基础医学院全军免疫学研究所
2.400038 重庆，陆军军医大学（第三军医大学）：药学与检验医学系药物分析学教研室
- 作者简介：
[王莉，E-mail：liwang118@tmmu.edu.cn WANG Li, E-mail: liwang118@tmmu.edu.cn
- 基金信息：国家自然科学基金面上项目(81871301)
DOI：10.16016/j.1000-5404.202011146
中图分类号： R322.57;R363.13;R394.3收稿：2020-11-16，
修回：2021-01-13，
纸质出版：2021-04-15
- 稿件说明：
移动端阅览
李向前, 王丽娜, 张梦军, 等. 高糖环境对胰岛β细胞系转录组表达谱的影响[J]. 第三军医大学学报, 2021,43(7):584-592.
Xiangqian LI, Lina WANG, Mengjun ZHANG, et al. Effect of high glucose environment on transcriptome expression profile of islet β cell line[J]. Journal of Third Military Medical University, 2021, 43(7): 584-592.
李向前, 王丽娜, 张梦军, 等. 高糖环境对胰岛β细胞系转录组表达谱的影响[J]. 第三军医大学学报, 2021,43(7):584-592. DOI： 10.16016/j.1000-5404.202011146.
Xiangqian LI, Lina WANG, Mengjun ZHANG, et al. Effect of high glucose environment on transcriptome expression profile of islet β cell line[J]. Journal of Third Military Medical University, 2021, 43(7): 584-592. DOI： 10.16016/j.1000-5404.202011146.
摘要
目的
2
研究高浓度葡萄糖刺激因素对1型糖尿病（type 1 diabetes
T1D）模型小鼠来源的胰岛β细胞系全转录组表达谱的影响，探讨高糖环境因素参与T1D发病的可能机制。
方法
2
将处于对数生长期的非肥胖糖尿病（non-obese diabetic
NOD）小鼠来源的胰岛β细胞系NIT-1细胞分为对照组（NIT1）和高糖处理组（HG），采用RNA-Seq技术进行全转录组测序，获取差异表达基因（differentially expressed genes
DEGs），并对DEGs进行GO注释以及KEGG Pathway富集性分析。
结果
2
NIT1组和HG组之间共检测到DEGs 5 548个；其中HG组上调DEGs 2 701个，下调DEGs 2 847个，其中上调DEGs显著富集在内质网应激、内质网蛋白加工处理、泛素化介导的蛋白质降解、自噬、凋亡等途径；下调基因主要富集在核糖体、代谢、生物合成、细胞周期、DNA复制等途径。HG组部分关键T1D自身抗原的mRNA表达显著增加。
结论
2
高糖诱导胰岛β细胞系全转录组显著变化，表现出胰岛β细胞自身抗原的表达及抗原加工、处理能力增强，提示高糖因素可能与诱导β细胞自身免疫反应及T1D的发生、发展有关。
Abstract
Objective
2
To study the effect of high glucose concentration on the transcriptome expression profile of islet β cells derived from type 1 diabetes (T1D) mice and to explore the possible mechanism of high glucose environment in the pathogenesis of T1D.
Methods
2
The non-obese diabetic (NOD) mice-derived islet β cell line NIT-1 in logarithmic growth phase were divided into high glucose-treated (HG) and control (NIT1) group. The cells in the NIT1 group were routinely cultured in F-12K medium
while HG group were treated with 20 mmol/L glucose. Whole transcriptome profile was analyzed using RNA-sequencing technology to obtain the differentially expressed genes (DEGs). And the DEGs were further analyzed by GO annotation and KEGG pathway enrichment analysis.
Results
2
A total of 5 548 DEGs were detected between the NIT1 group and HG group. Among them
2 701 DEGs were up-regulated in the HG group
which were significantly enriched in endoplasmic reticulum stress
endoplasmic reticulum protein processing
ubiquitin-mediated protein degradation
autophagy and apoptosis pathways. And the 2 847 down-regulated genes were mainly concentrated in ribosome
metabolism
biosynthesis
cell cycle and DNA replication. Moreover
the mRNA levels of some important T1D auto-antigens were significantly increased in the HG group.
Conclusion
2
High glucose environment significantly changes the whole-transcriptome profile of islet β cells
and promotes the abilities of antigen processing and presentation
suggesting that high glucose might be associated with the induction of autoimmune response of islet cells and the incidence and development of T1D.
关键词
Keywords
references
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