The Role of miR301a and Its Potential as a Biomarker for Prediction of Liver Transplant Rejection

Liver transplantation is an effective therapy for end-stage liver diseases and the outcomes are determined by graft rejection and dysfunction. Acute rejection (AR) may occur in up to 80% of liver allografts during the first post-operative year. The mechanisms are some of the most important areas of study in the transplantation field. In our Lab., we have successfully established experimental orthotopic liver transplantation (OLT) models including DA-PVG natural tolerance model, which spontaneously accept donor DA liver without immunosuppressive treatments and DA-LEW AR model, which usually reject donor DA liver within 14 days. By using these well-established animal models, we have identified miR-301a as an AR-specific microRNA in DA-LEW rejecting liver allografts after OLT. However, little is known about the roles of miR-301a in the rejection process after liver transplantation. In this proposal, therefore, we will shift our focus on miR-301a in liver allograft rejection. In addition, it is better to identify additional circulating microRNAs for non-invasive diagnosis of AR in clinical settings. To understand the immunological aspects of hepatic miR-301a in the course of liver transplant rejection, we will propose four strategies: 1. Effects of miR-301a expression on primary hepatocytes and immune phenotyping. 2. Clinical significance of miR-301a expression in the liver and peripheral blood for classification of AR or abnormal liver function. 3. Characterization of circulating microRNAs and targeted mRNAs in the course of AR. 4. Establishment of miR-301a targeted therapy in experimental liver transplantation. Taken together, specific aims of this proposal are to identify and verify AR-specific hepatic and circulating microRNAs in experimental and clinical OLT and to explore underlying mechanisms of these microRNAs in the course of liver transplant rejection.

Project ID:PC10408-1728
External Project ID:MOST104-2320-B182-030