Acute rejection results in a unique signature of microRNAs (169.22)

Abstract

Abstract MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the post-transcriptional expression of genes. Little is known about the roles of specific miRNAs in alloimmune responses. Groups of syngeneic and allogeneic recipients of heart transplants were sacrificed on day 7 post-transplant and heart grafts and spleens obtained. Graft infiltrating lymphocytes (GIL) and peripheral blood lymphocytes (PBL) were isolated on post-transplant day 5. MicroRNAS were profiled using TaqMan microfluidic cards. Forty-two miRNAs were increased and 32 were decreased (p<0.05) in allogeneic heart grafts as compared to syngeneic. To determine if these miRNAs were expressed by lymphocytes or heart tissue, we profiled the GIL and determined that 22 miRNAs were increased and 52 decreased. There was less differential expression seen in spleen and PBL with 11 and 9 miRNAs changed respectively. Seventeen miRNAs were selected for validation by qPCR. The miRNAs, miR-7a and miR-182 were significantly increased in the heart graft, GIL, and PBL indicating that acute rejection results in specific profile of miRNAs in both the graft and the periphery. Further studies analyzing the targets of the miRNAs associated with graft rejection may lead to novel therapeutics and diagnostics.