Downregulation of cyclic microRNA-199a-3p may be early warning index of acute rejection after liver transplantation

Abstract

Objective To screen microRNAs (miRNA, miR) in the venous blood that could prompt for the occurrence of acute rejection after liver transplantation. Methods Forty male Lewis rats and eighty male BN rats were randomly divided into experimental groups by random number method according to their body weight, and rat liver transplantation model was established by modified two-cuff method. The immune tolerance BN rats [immune tolerance (IT) group] were transplanted with livers from other BN rats. BN rats in the acute immunological rejection group [acute rejection (AR) group] were transplanted with livers from Lewis rats. The immune intervention group [transforming growth factor-β1 (TGF-β1) immature dendritic cells (imDCs) group] were operated as AR group, and intraperitoneally injected 2×106 imDCs over-expressed TGF-β1 5 days before surgery. MicroRNA microarray was used to detect the expression of miRNAs in the venous blood 7 day after operation. The differential expression levels of miRNAs were analyzed by bioinformatics software, and [fold change FC(abs)]>2.0 served as the threshold value. Results Compared with IT group, miR-199a-3p, miR-331-3p and miR-203a-3p were significantly down-regulated [for miR-199a-3p, FC(abs)=27.997, P=0.017; for miR-331-3p, FC(abs)=5.403, P=0.034; for miR-203a-3p, FC(abs)=24.593, P=0.022]. Compared with TGF-β1 imDCs group, miR-199a-3p, miR-331-3p and miR-203a-3p were significantly down-regulated [for miR-199a-3p, FC(abs)=459.128, P=0.000; for miR-331-3p, FC(abs)=9.877, P=0.031; for miR-203a-3p, FC(abs)=26.894, P=0.020). The differential expression of miR-199a-3p among groups was the most significant [FC(abs)=459.128]. Conclusion Downregulation of miR-199a-3p in peripheral blood of rats after liver transplantation may be the early warning of AR. Key words: Liver transplantation; MicroRNA; Acute rejection; Immature dendritic cells