Microarray analysis for differentially expressed genes of patients undergoing total knee arthroplasty with ischemia preconditioning

Background

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.

Methods

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.

Results

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.

Conclusions

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.