基于蛋白相互作用网络探讨2019-nCoV受体ACE2与糖尿病靶点的相互关系

Interrelationship between 2019-nCoV receptor ACE2 and diabetes mellitus target based on protein interaction network

目的:通过蛋白相互作用网络探讨糖尿病靶点与新型冠状病毒(2019-nCoV)受体血管紧张素转换酶2(ACE2)的关系,为临床用药提供新思路。方法:从GeneCards、OMIM数据库获取糖尿病靶点,将关联分数超过10的靶点纳入,并手动添加ACE2蛋白。通过String获取初始蛋白相互作用关系网络,将其导入Cytoscape3.7.1软件,筛选出与ACE2直接相关的蛋白靶点作为最终分析的靶标,再次导入String,得到待分析蛋白相互作用关系网络,并对其进行模块识别及GO分析和KEGG通路分析。通过对ACE2所在模块评分,分析其对整个网络的影响。结果:最终从糖尿病靶点中筛选得到19个ACE2相关蛋白,通过聚类分析发现3个功能模块,模块涉及G蛋白藕联受体结合、抗氧化剂活性、胰岛素样生长因子受体结合等生物过程,主要涉及的信号通路有肾素-血管紧张素系统信号通路、2型糖尿病信号通路,以及FOXA2信号通路。评分结果显示,模块1内REN、AGT、INS、NOS3、IL6、CRP的评分最高。结论:ACE2与糖尿病关键蛋白有广泛的联系,COVID-19可能冲击糖尿病患者RAS,导致糖尿病合并COVID-19患者的高死亡率,临床可考虑使用RAS抑制剂减轻COVID-19感染对糖尿病患者的影响。

Objective Exploring the relationship between diabetes mellitus targets and ACE2 of the receptor of novel coronavirus(2019-nCoV)through a protein interaction network to provide new perspectives for clinical use.Methods Diabetes mellitus targets were obtained from the GeneCards and OMIM databases.Targets with a relevance score exceeding 10 were included,and ACE2 protein was manually added.The initial protein interaction network was obtained through String and then imported into Cytoscape 3.7.1.We selected the protein targets directly related to ACE2 as the target of the final analysis and imported them into String again in order to obtain the protein interaction network.Module identification,GO analysis and KEGG pathway analysis were performed respectively.The impact of ACE2 on the entire network was analyzed by scoring the module where it located.Results 19 ACE2-related proteins were finally selected from diabetes mellitus targets.Three functional modules were found through the cluster analysis.These modules involved G protein-coupled receptor binding,antioxidant activity,and insulin-like growth factor receptor binding.The main signal pathways involved were the renin angiotensin system signal pathway,the type 2 diabetes mellitus signal pathway,and the FOXA2 signal pathway.The scoring results showed that REN,AGT,INS,NOS3,IL6,and CRP scored the highest.Conclusions ACE2 is widely associated with diabetes mellitus key proteins.COVID-19 may impact RAS of diabetes mellitus patients then induce serious complications.Clinical use of RAS inhibitors may reduce the impact of COVID-19 infection on diabetes mellitus patients.