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Prof. Dr. Jochen Fries

Kidney Research

Endothlein-1 induced signalling leading to miRNA15a induction and truncated MAPKp38alpha, Mxi-2, being a transcription factor involved in p53 downregulation and proliferation.

The research group Fries has a longstanding expertise in the role of microRNAs in renal disease. We described a new role for miRNA in generating two intron included, C-terminal truncated and biologically active proteins (Mxi-2 and Vim3), with Mxi-2 acting as transcription factor and Vim-3 being a new marker for benign renal tumors, oncocytomas. This also resulted in a signal pathway with a feedback loop for Endothelin-1 (ET-1) induction of miRNA15a in the nucleus via ET-B receptor mediated downregulation of PKCalpha, where upregulated urine levels can be detected in proteinuric renal diseases and in renal cancer. MiRNA133a was found as indicator for nephrotoxicity after Cyclosporine A treatment or in proteinuric diseases (incl. the Adriamycin animal model), with respective treatment options by ET-1 B receptor blockade as demonstrated in a rat ETB-receptor knock-out model after 5/6 nephrectomy.