已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

[Analysis of hub genes and molecular mechanisms in non-alcoholic steatohepatitis based on the gene expression omnibus database].

小桶 脂肪性肝炎 基因 脂肪肝 基因表达 微阵列 生物 疾病 DNA微阵列 计算生物学 生物信息学 医学 遗传学 内科学 基因本体论
作者
L.Y. Li,Jiajing Wu
出处
期刊:PubMed 卷期号:101 (40): 3317-3322 被引量:1
标识
DOI:10.3760/cma.j.cn112137-20210416-00913
摘要

Objective: To explore the hub genes and mechanisms in the pathological process of non-alcoholic steatohepatitis (NASH) by bioinformatics methods. Methods: Microarray datasets GSE89632 were downloaded from the Gene Expression Omnibus (GEO) database, which including 20 simple non-alcoholic fatty liver disease patients, 19 NASH patients and 24 healthy control individuals. The differentially expressed genes (DEGs) in patients with simple non-alcoholic fatty liver disease and NASH were compared with healthy control individuals respectively, and the intersection of the two groups of DEGs was taken. GO functional annotation and KEGG pathway enrichment analysis of DEGs were performed with DAVID 6.8 and KOBAS 3.0 separately. Protein-protein interaction network (PPI) was constructed by STRING database, then the mRNA hub genes were selected by Cytoscape software. The Attie Lab Diabetes database was used to verify the relative expression of hub genes mRNA in the liver of 4 groups of C57BL/6 mice (4-week-old normal group, 4-week-old obese group, 10-week-old normal group and 10-week-old obese group, 5 mice in each group). Spearman's correlation analysis was performed to analyze the correlation between hub gens and prognostic clinical parameters. Results: From the GSE89632 dataset, 365 common DEGs (115 up-regulated genes and 250 down-regulated genes) were identified in patients with simple non-alcoholic fatty liver disease and NASH patients compared with control individuals. GO analysis showed that DEGs were mainly enriched in biological processes such as inflammatory response and immune response. KEGG pathway analysis showed that up-regulated genes were mainly enriched in cholesterol metabolism, bile secretion and fat digestion and absorption signal pathways. Down-regulated genes were mainly enriched in interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, advanced glycation end products and their receptors of diabetic complications. Seven key hub genes were identified by PPI analysis, which were FOS, EGR1, FOSB, JUNB, FOSL1, MYC and NR4A1.The mRNA relative expression levels of EGR1 and JUNB in the liver of 10-week-old obese mice were lower than those of normal mice (P<0.05).The relative expression levels of NR4A1 in the liver of obese mice at 4-and 10-week-old were lower than those of normal mice at the same age (P values<0.05). Spearman's correlation analysis showed that the expression of EGR1 was negatively correlated with the degree of hepatic steatosis (r=-0.785, P<0.001).The expression levels of FOSB, MYC and NR4A1 were negatively correlated with the level of alanine aminotransferase (r=-0.649, -0.597 and-0.580 respectively, all P values<0.001). Conclusion: EGR1, FOSB, MYC, JUNB and NR4A1 might be the hub genes in the pathological process of NASH and the inflammatory and immune response in hepatocytes, IL-17 signaling pathway and TNF signaling pathway might be the key molecular mechanisms in the occurrence and development of NASH.目的: 采用生物信息学方法探索与非酒精性脂肪肝炎(NASH)病理进程相关的核心基因及分子机制。 方法: 由基因表达数据库(GEO)下载基因表达数据集GSE89632,包含单纯非酒精性脂肪肝患者、NASH患者和健康对照分别为20、19和24例,筛选单纯非酒精性脂肪肝患者和NASH患者相对于健康对照的差异表达基因(DEGs),对两组DEGs取交集。采用DAVID 6.8数据库对DEGs进行GO功能富集分析,采用KOBAS 3.0数据库对DEGs进行京都基因与基因组百科全书(KEGG)信号通路分析。利用STRING数据库构建DEGs蛋白相互作用网络(PPI),采用Cytoscape软件筛选核心基因。利用Attie Lab 糖尿病数据库验证核心基因在4组C57BL/6小鼠(分别为4周龄正常组、4周龄肥胖组、10周龄正常组和10周龄肥胖组,每组各5只)肝脏中mRNA相对表达量。分析核心基因和预后临床指标的相关性。 结果: 由GSE89632数据集筛选出单纯非酒精性脂肪肝患者和NASH患者相对于健康对照的365个共同DEGs,其中上调和下调基因分别为115和250个。GO分析显示DEGs主要富集于炎症反应和免疫应答等生物过程。KEGG信号通路分析显示:上调基因主要富集于胆固醇代谢、胆汁分泌和脂肪的消化吸收等信号通路;下调基因主要富集于白细胞介素-17信号通路、肿瘤坏死因子信号通路和糖尿病并发症的晚期糖基化终末产物及其受体等信号通路。PPI分析筛选出7个关键核心基因,分别为FOS、EGR1、FOSB、JUNB、FOSL1、MYC和NR4A1。10周龄肥胖小鼠肝脏中EGR1和JUNB的mRNA相对表达量均低于10周龄正常小鼠,均P<0.05;4和10周龄肥胖小鼠肝脏中NR4A1相对表达量均低于同周龄正常组小鼠,均P<0.05。EGR1基因表达水平与肝脏脂肪变性程度呈负相关(r=-0.785,P<0.001)。FOSB、MYC和NR4A1基因表达水平与血液谷丙转氨酶水平呈负相关(r=-0.649、-0.597和-0.580,均P<0.001)。 结论: EGR1、FOSB、MYC、JUNB和NR4A1等基因可能为NASH病理进程中的核心基因,肝细胞内炎症反应和免疫应答、白细胞介素-17信号通路和肿瘤坏死因子信号通路可能是NASH病理进程的关键分子机制。.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
干羞花完成签到,获得积分10
2秒前
小二郎完成签到,获得积分10
3秒前
5秒前
dai发布了新的文献求助10
5秒前
11秒前
11秒前
研友_8RlG1n完成签到,获得积分10
13秒前
诗梦完成签到,获得积分10
16秒前
遇more完成签到 ,获得积分10
19秒前
TS发布了新的文献求助10
19秒前
vv完成签到 ,获得积分10
21秒前
子焱发布了新的文献求助10
22秒前
23秒前
完美世界应助jinni采纳,获得10
28秒前
myelin发布了新的文献求助10
29秒前
可爱的函函应助子焱采纳,获得10
30秒前
zr92驳回了mmmm应助
34秒前
英勇明雪完成签到,获得积分10
36秒前
41秒前
汉堡包应助科研通管家采纳,获得10
43秒前
小马甲应助科研通管家采纳,获得10
43秒前
斯文败类应助科研通管家采纳,获得10
43秒前
shinysparrow应助科研通管家采纳,获得100
43秒前
43秒前
田様应助富马酸小小采纳,获得20
44秒前
二十发布了新的文献求助30
45秒前
47秒前
52秒前
jinni发布了新的文献求助10
52秒前
玲龙雨完成签到 ,获得积分10
54秒前
科研通AI2S应助cfyoung采纳,获得10
54秒前
Echodeng完成签到,获得积分10
55秒前
陈独秀完成签到,获得积分10
56秒前
开朗的达完成签到,获得积分10
59秒前
风-FBDD完成签到,获得积分10
1分钟前
共享精神应助hong采纳,获得10
1分钟前
1分钟前
1分钟前
1分钟前
魏魏发布了新的文献求助10
1分钟前
高分求助中
Evolution 10000
ISSN 2159-8274 EISSN 2159-8290 1000
Becoming: An Introduction to Jung's Concept of Individuation 600
Ore genesis in the Zambian Copperbelt with particular reference to the northern sector of the Chambishi basin 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3161905
求助须知:如何正确求助?哪些是违规求助? 2813139
关于积分的说明 7898729
捐赠科研通 2472140
什么是DOI,文献DOI怎么找? 1316366
科研通“疑难数据库(出版商)”最低求助积分说明 631278
版权声明 602129