RETRACTED ARTICLE: Microarray analysis for differentially expressed genes of patients undergoing total knee arthroplasty

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RESEARCH ARTICLE

Open Access

Microarray analysis for differentially expressed genes of patients undergoing total knee arthroplasty with ischemia preconditioning Jianguang Wang1,2, Zhengdong Cai3,4,5* and Junjian Liu2,5*

Abstract 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. Keywords: Ischemia preconditioning, microRNA, Transcriptional factor, Protein-protein interaction network

Background Many surgical procedures involve prolonged ischemia of organs or tissues which can lead to sever postoperative complications, including dysfunction and necrosis [1]. In order to prevent ischemia-reperfusion injury, Murry et al. first documented the protective effect of ischemia preconditioning (IPC) in 1986 [2]. IPC has been proved as an extremely powerful method of protecting tissues against subsequent sustained ischemia insults [3] when it is firstly subjected to short bursts of ischemia and reperfusion. This method is universally applicable in * Correspondence: [email protected]; [email protected] 3 The Affiliated Shanghai No.1 People’s Hospital, Nanjing Medical University, Shanghai 200080, China 2 Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China Full list of author information is available at the end of the article

modulating ischemia-reperfusion injury to tissues including the myocardium [4], brain [5], liver [6], lung [7], kidney [8], intestine [9], and skeletal muscle [10]. IPC is thought to provide protection by inducing tissues’ toleran