Transcriptional changes in orthotopic liver transplantation and ischemia/reperfusion injury

Abstract

BackgroundThere are few effective targeting strategies to reduce liver ischemia-reperfusion injury (IRI), which is one of the reasons for the poor prognosis of liver transplant recipients.MethodsA systematic approach combining gene expression with protein interaction (PPI) network was used to screen the characteristic genes and related biological functions of post-transplant. Differentially expressed genes (DEGs) between IRI+ and IRI- were identified. Logistic regression model and receiver operating characteristic (ROC) curve were used to identify potential target genes of IRI. The expression of key genes was verified by qRT-PCR and Western-blot experiments. Finally, the ssGSEA was used to identify the immune cell infiltration in patients with IRI.ResultsThe 283 common DEGs in GSE87487 and GSE151648 were mainly related to apoptosis and IL-17 signaling pathway. Through PPI network and logistic regression analysis, we identified that IL6, CCL2 and CXCL8 may be involved in the ischemia/reperfusion (IR) process. In addition, 32 genes were showed associated with IRI through inflammatory and metabolic pathways. Among the key genes identified, the differential expression of AGBL4, CILP2 and IL4I1 was verified by molecular experiments. Th17 cells of differentially infiltrated immune cells were positively correlated with CILP2 and IL4I1. The difference of Th17 cells between IRI+ and IRI- was verified by flow cytometry.ConclusionThe study showed that AGBL4, CILP2 and IL4I1 were associated with IRI. Th17 cells may be associated with the regulation of IRI by key genes. These genes and related pathways may be targets for improving IRI.