MicroRNA-142-5p is Up-regulated on Allogeneic Immune Responses and Up-regulates MHC Class II Expression in Human Umbilical Vein Endothelial Cells

Abstract

Purpose. MicroRNA could be biomarker and therapeutic target for rejection. The aim of this study was to investigate the role of miR-142-5p in allogeneic immune responses using in vitro and in vivo models. Materials and Methods. Primary and immortalized human umbilical vein endothelial cells (HUVECs) were cultured with unrelated blood mononuclear cells to induce allogeneic immune responses. Syngeneic and allogeneic skin graft was performed in mice. Flow cytometry, quantitative reverse transcriptionepolymerase chain reaction, and Western blotting was performed to understand the underlying mechanisms. Results. miR-142-5p was up-regulated in primary HUVEC and a HUVEC line when allogeneic immune responses were elicited. miR-142-5p was also up-regulated in the murine allogeneic skin graft. Overexpression of miR-142-5p in HUVEC increased the expression of HLA-ABC and HLA-DR additively to allogeneic immune responses, suggesting a possible increase in alloantigen presentation. Inhibition of miR-142-5p reduced the expression of HLA-DR. ZEB1, a putative target gene of miR-142-5p, was down-regulated in HUVEC on allogeneic immune response as well as in murine allogeneic skin graft. Conclusion. These results suggest that the up-regulation of miR-142-5p on allogeneic immune response might facilitate endothelial activation to exacerbate rejection.