Wang Jianguang, Cai Zhengdong, Liu Junjian
J Orthop Surg Res. 2014;9(1):133. doi: 10.1186/s13018-014-0133-0. Epub 2014 Dec 12.
Ischemia preconditioning (IPC) has been proved as a powerful method of protecting tissues against ischemia reperfusion insults. We aimed to elucidate the mechanism of IPC in ischemia reperfused tissues.
GSE21164 containing 16 muscle biopsies taken from the operative knee of four IPC-treated patients and four control at the onset of surgery (T¿=¿0) and 1 h into surgery (T¿=¿1) undergoing primary total knee arthroplasty was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between IPC group and control were screened with Limma package in R language. KEGG pathway enrichment analysis was performed by the DAVID online tool. Meanwhile, potential regulatory microRNAs (miRNAs) for downregulated DEGs and targets of transcription factors for upregulated DEGs were screened out. Based on the above DEGs, protein-protein interaction (PPI) networks were constructed by the STRING software.
Significantly upregulated DEGs at T1 were mainly enriched in asthma and p53 signaling pathway. Meanwhile, significantly enriched transcriptional factor NOTCH1 at T1 and GABP at T0 were obtained. Moreover, miRNA analysis showed that targets of miR141/200a were enriched in downregulated DEGs both at T0 and T1. Mostly, RPA1 and JAK2 in PPI network at T1 were with higher degree.
In our study, obtained DEGs, regulatory transcriptional factors, and miRNA might play a vital role in the protection of ischemia reperfusion injury. This finding will provide a deeper understanding to the mechanism of IPC.
缺血预处理(IPC)已被证明是保护组织免受缺血再灌注损伤的有效方法。我们旨在阐明IPC在缺血再灌注组织中的作用机制。
从基因表达综合数据库(GEO)下载GSE21164数据集,其中包含来自4例接受IPC治疗患者和4例对照患者手术开始时(T = 0)及手术1小时后(T = 1)手术膝关节的16份肌肉活检样本,这些患者均接受初次全膝关节置换术。使用R语言中的Limma软件包筛选IPC组和对照组之间的差异表达基因(DEG)。通过DAVID在线工具进行KEGG通路富集分析。同时,筛选出下调DEG的潜在调控微小RNA(miRNA)和上调DEG的转录因子靶点。基于上述DEG,使用STRING软件构建蛋白质-蛋白质相互作用(PPI)网络。
T1时显著上调的DEG主要富集于哮喘和p53信号通路。同时,在T1时获得显著富集的转录因子NOTCH1,在T0时获得显著富集的GABP。此外,miRNA分析表明,miR141/200a的靶点在T0和T1时均富集于下调的DEG中。在T1时的PPI网络中,RPA1和JAK2大多具有较高的连接度。
在我们的研究中,获得的DEG、调控转录因子和miRNA可能在缺血再灌注损伤的保护中发挥重要作用。这一发现将为IPC的机制提供更深入的理解。