Glomerular miRNA Expression in the Fischer to Lewis Rat Model of Acute Humoral Rejection.

Abstract

Acute humoral rejection is currently the most important diagnostic and therapeutic problem in renal transplantation. The Fischer to Lewis rat model is a well established model of acute humoral rejection due to MHC and non-MHC alloantibodies. In order to identify diagnostically useful glomerular miRNA expression patterns and to identify novel pathogenetic concepts and therapeutic targets we quantififed the glomerular miRNA expression of this model. 6 weeks after life-sustaining transplantation without immunosuppression 8 allografts were harvested for histologic examination and glomerular miRNA quantification by RT-PCR. Histologic changes and miRNA expression patterns were correlated and compared to 8 isografts. Glomerular capillaries contained significantly more monocytes in allografts than in isografts, consistent with transplant glomerulitis. In allograft glomeruli miR-451 and miR-192 were significantly downregulated compared to isografts. Both were inversely correlated with glomerular C4d deposition and monocyte content. With miR-192 and miR-451 we identified two micro-RNAs which are downregulated in the glomeruli of a rat model of acute humoral rejection. Whereas little is known about miR-192, miR-451 is known to be involved in inflammation. Both could be valid target molecules in acute humoral rejection. Our next projects will determine the exact cell type expressing both miRNAs, their relevance for human acute humoral rejection, their function and potential as therapeutic targets.