Expression and predictive functional profiles on MicroRNAs data in Vascularized Composite Allotransplantation Acute Rejection

Abstract Aim: To investigate the mechanisms of acute rejection for vascularized composite allotransplantation (VCA) using microRNAs (miRNAs) differential expression in a VCA animal model.Methods: Three brown Norway rats were used as transplant donors and three Lewis rats as VCA receptors. The changes were divided into different stages before and after transplantation in Lewis rats. The appearance changes of all subjects were recorded. Also, histological evaluations were performed on all recipients, and the microRNAs expression was analyzed when acute immune rejection occurred. Then, GO and KEGG Pathway analyses were employed to predict miRNA targets. Finally, differentially expressed miRNAs were detected by RT-qPCR.Results: Compared to pre-operation, 22 miRNAs were screened for significantly different expressions. Among them, nine were upregulated and 13 were downregulated in skin tissues. The RT-qPCR results revealed that rno-miR-340-5p and rno-miR-21-5p were significantly upregulated and enriched in the PI3K-Akt signaling pathway. Moreover, rno-miR-145-5p and rno-miR-195-5p were significantly downregulated, and most of their target genes were enriched in the Hippo signaling pathway. The histological evaluations showed that, after VCA, the skin tissue presented severe acute rejection.Conclusion: Overall, the miRNAs rno-miR-340-5p, rno-miR-21-5p, rno-miR-145-5p, and rno-miR-195-5p were significantly regulated during VCA acute rejection. These miRNAs are potential biomarkers for objective, early, and minimally invasive rejection diagnosis.