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对2型糖尿病食蟹猴肝脏转录组的RNA测序分析。

RNA-seq analysis of the transcriptome of the liver of cynomolgus monkeys with type 2 diabetes.

作者信息

Li Xinyu, Lin Zijing, Zhan Xiaorong, Gao Jie, Sun Lijie, Cao Yan, Qiu Hui

机构信息

Department of Endocrinology, First Affiliated Hospital Harbin Medical University, Harbin, Heilongjiang, PR China; Department of Pharmacology, The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang, PR China.

Department of Endocrinology, First Affiliated Hospital Harbin Medical University, Harbin, Heilongjiang, PR China.

出版信息

Gene. 2018 Apr 20;651:118-125. doi: 10.1016/j.gene.2018.02.010. Epub 2018 Feb 4.

Abstract

Genetic and environmental factors such as high-fat diet are involved in the development of type 2 diabetes mellitus (T2DM). Cynomolgus monkey shares similar genetic makeup, tissue structures, physiology and metabolic function to human. This study aimed to establish T2DM model in cynomolgus monkey and compare expression profiles of hepatic genes and their associated pathways in normal cynomolgus monkeys and those with T2DM. We employed RNA-seq technique and identified 1451 differentially expressed genes (DEGs) with a false discovery rate (FDR) of 0.1% between normal and T2DM animals. KEGG pathway analysis revealed that DEGs were associated with 12 KEGG pathways (P < 0.05). Two of these pathways were associated with metabolism and five were related to immunity. Unexpected, we found ECM-receptor interaction pathway. In conclusion, our data suggest that three major pathways may be implicated in the development of T2DM, including steroid biosynthesis, immune response and ECM. Further characterization of these pathways may provide new targets for the prevention and therapy of T2DM.

摘要

遗传和环境因素,如高脂饮食,都与2型糖尿病(T2DM)的发生发展有关。食蟹猴在基因组成、组织结构、生理和代谢功能方面与人类相似。本研究旨在建立食蟹猴T2DM模型,并比较正常食蟹猴和T2DM食蟹猴肝脏基因的表达谱及其相关通路。我们采用RNA测序技术,在正常和T2DM动物之间鉴定出1451个差异表达基因(DEG),错误发现率(FDR)为0.1%。KEGG通路分析显示,DEG与12条KEGG通路相关(P<0.05)。其中两条通路与代谢相关,五条与免疫相关。出乎意料的是,我们发现了细胞外基质受体相互作用通路。总之,我们的数据表明,T2DM的发生发展可能涉及三条主要通路,包括类固醇生物合成、免疫反应和细胞外基质。对这些通路的进一步表征可能为T2DM的预防和治疗提供新的靶点。

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