摘要
目的进一步理解单纯肥胖发展为二型糖尿病(T2DM)的潜在机制,探讨色素上皮衍生因子(PEDF)在该过程中的影响与作用。方法检索获取美国国家生物技术信息中心基因表达综合数据库并获取人胰岛组织的基因表达芯片GSE50398数据集,筛选样本差异表达基因数据进行富集分析并筛选核心靶点,利用基因集富集分析方法进行基因本体(GO)富集分析以及京都基因与基因组百科全书(KEGG)信号通路分析,对相关基因RNA测序结果进行Spearman R相关性分析。结果通过相关疾病数据库搜索筛选单纯肥胖和T2DM合并肥胖相关靶点分别为836和53个,其中共同差异靶点28个。两组差异表达基因都显著富集丝裂原活化蛋白激酶(MAPK)信号通路,潜在靶基因显著富集于涉及成骨细胞分化、胰高血糖素分泌及调节胰高血糖素分泌的生物过程。肥胖患者胰岛PEDF表达上升,PEDF与人胰岛功能相关基因PDX1、MAFA、INS和SLC2A2表达呈负相关关系(r=-0.5506、-0.5287、-0.4635、-0.5930,P<0.0001)。结论MAPK信号通路等同时在单纯肥胖及T2DM合并肥胖中起到调控作用。胰高血糖素分泌等生物过程以及肥胖状态下升高的PEDF可能抑制胰岛功能相关基因作用于肥胖发展为二型糖尿病的过程。
Objective To further understand the mechanism of developing type 2 diabetes mellitus from simple obesity,and explore the influence and role of pigment epithelium-derived factor(PEDF)in this process.Methods The gene expression of islet tissue chip GSE50398 data sets were retrieved from the national center for biotechnology information comprehensive gene expression database,and analyzed for the differentially expressed genes and filter core targets by gene oncology(GO)enrichment and kyoto encyclopedia of genes and genomes(KEGG)pathway analysis.Spearman R correlation analysis was performed on related genes.Results A total of 836 and 53 targets related to obesity alone and type 2 diabetes mellitus accompanied with obesity were screened by searching related disease databases;among which,28 were common.The differentially expressed genes in both groups were significantly enriched in mitogen-activated protein kinase(MAPK)signaling pathway,and the potential target genes were significantly enriched in biological processes involved in osteoblast differentiation,glucagon secretion and regulation of glucagon secretion.The expression of PEDF increased in obese patients,and PEDF was negatively correlated with the expression of human islet function-related genes PDX1,MAFA,INS and SLC2A2(r=-0.5506,-0.5287,-0.4635,-0.5930,P<0.0001).Conclusions MAPK signaling pathway might play a regulatory role in obesity alone and type 2 diabetes mellitus accompanied with obesity.Biological processes such as glucagon secretion and increased PEDF in obesity might inhibit islet function-related genes in the progression of obesity to type 2 diabetes mellitus.
作者
谭艳丹
刘峻熙
赵溱
周倜
杨霞
高国全
齐炜炜
TAN Yan-dan;LIU Jun-xi;ZHAO Zhen;ZHOU Ti;YANG Xia;GAO Guo-quan;QI Wei-wei(Department of Biochemistry,Zhongshan School of Medicine,Sun Yat⁃sen University,Guangzhou,Guangdong 510080,China)
出处
《热带医学杂志》
CAS
2022年第3期301-305,448,共6页
Journal of Tropical Medicine
基金
国家自然科学基金(82070888,82070882,81770808)
广东省自然科学基金(2019A1515011810)
广东省区域联合基金重点项目(2019B1515120077)
广东省重点研发计划(2018B030337001)
关键词
肥胖
二型糖尿病
生物信息学
色素上皮衍生因子
Obesity
Type 2 diabetes mellitus
Bioinformatics
Pigment epithelium-derived factor
作者简介
谭艳丹(1997-),女,在读硕士研究生,研究方向:PEDF与2型糖尿病研究;通信作者:齐炜炜,E⁃mail:qiww3@mail.sysu.edu.cn
