目的 基于生物信息学研究手段探讨骨质疏松与脂代谢疾病的潜在关系.方法 分别以"骨质疏松""非酒精性脂肪肝""动脉粥样硬化""肥胖"和"糖尿病"为关键词在 GeneCards 数据库、在线孟德尔遗传(online mendelian inheritance in man,OMIM)数据库、Drugbank 数据库、药物靶点(therapeutic target database,TTD)数据库进行检索以收集疾病相关的靶点,取各疾病的交集靶点分别进行蛋白-蛋白互作网络构建、关键基因筛选、基因本体论(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)生物富集分析,同时构建基因调控网络以了解靶基因、药物、microRNAs、转录因子潜在的相互作用.结果 通过数据库分析共得到骨质疏松靶点 841 个,非酒精性脂肪肝靶点 1142 个,动脉粥样硬化靶点 696 个,肥胖靶点 717 个,糖尿病靶点 691 个,各数据集映射得到交集靶点 69 个,为骨质疏松和脂代谢疾病相关的关键靶点.经基因/蛋白相互作用检索搜查工具(search tool for the retrieval of interacting genes/proteins,STRING)数据库分析共得到 1372 条 GO 富集结果(P＜0.05)和 136 条 KEGG 富集结果(P＜0.05).在基因调控网络中筛选得到 10 种关键药物、83 个转录因子、82 个 microRNAs.结论 RAC-α 丝氨酸/苏氨酸-蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)、血清白蛋白(serum albumin,ALB)、胰岛素(insulin,INS)、白细胞介素 6(interleukin-6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF)、瘦素(leptin,LEP)、过氧化物酶体增殖物活化受体 γ(peroxisome proliferator-activated receptor gamma,PPARG)等核心交集靶点作用于 AMP 依赖的蛋白激酶[adenosine 5'-monophosphate(AMP)-activated protein kinase,AMPK]信号通路、低氧诱导因子 1(hypoxia inducible factor 1,HIF-1)信号通路、癌症相关信号通路且与脂肪酸代谢过程和免疫炎症过程密切相关.氨基葡萄糖(glucosamine)等核心药物可以为临床治疗骨质疏松与脂代谢类疾病的共病提供参考.
Investigation of the relationship between osteoporosis and lipid metabolism disorders based on bioinformatics
Objective To investigate the potential mechanism and relationship between osteoporosis and abnormal lipid metabolism disorders based on bioinformatics analysis.Methods The GeneCards,OMIM,Drugbank and TTD databases were used to screen disease-related targets with the key words"osteoporosis","obesity","atherosclerosis","nonalcoholic fatty liver disease"and"diabetes".The overlapped targets were finally selected to construct protein-protein interaction network,screen hub genes and perform GO and KEGG enrichment analysis.The gene regulatory networks were constructed to explore the potential relationship among target gene,drug,microRNAs and transcription factors.Results A total of 841 target genes for osteoporosis,1142 for nonalcoholic fatty liver disease,696 for atherosclerosis,717 for obesity and 691 for diabetes was collected as disease-related target datasets.The 69 overlapped targets were selected for further analysis.Based on the STRING database,GO enrichment analysis showed 1372 terms and KEGG analysis showed 136 signaling pathways(P＜0.05).Ten drugs,83 transcription factors and 82 microRNAs were obtained according to the results of gene regulatory network analysis.Conclusions The core overlapped targets such as AKT1,ALB,INS,IL-6,TNF,LEP and PPARG were enriched on AMPK signaling pathway,HIF-1 signaling pathway,and pathways associated with cancers.Tight relationships with fatty acid metabolic process and immune/inflammatory processes were shown.Drugs including glucosamine could provide references for the clinical treatment of comorbidity with osteoporosis and abnormal lipid metabolism disorders.
OsteoporosisLipid metabolism disordersComputational biologyAMP-Activated Protein Kinases
NETL
NSTL
万方数据
维普
