Translational characterization of hepatic miR-301a as a biomarker for acute rejection in experimental and clinical liver transplantation. Rattus norvegicus

Using a rat orthotopic liver transplantation (OLT) model and microarray, we compared the expression profiles of microRNAs in naïve and AR livers at day 7 after OLT obtained from the rats with short-term (60 days, DA-PVG) survival fate. AR-related microRNAs and pro-inflammatory cytokines were validated by using a quantitative real-time PCR. AR-related microRNA-mediated inflammatory responses were evaluated by overexpression of a target microRNA in rat primary hepatocytes. Human liver biopsies from recipients with AR or abnormal liver function were used for clinical verification. The microarray revealed that miR-301a was significantly upregulated in lethal AR livers of DA-LEW, while it was comparable to the naïve livers in DA-PVG, which spontaneously overcomes AR. Overall design: OLT was carried out following the technique previously described by Kamada et al. in the following combinations: DA donor liver into PVG (DA-PVG; natural tolerance model with long-term (>60 days) and DA donor liver into LEW (DA-LEW; AR model with short-term (<14 days).