Project Details
Projekt
Role of Ubiquitin C-Terminal Hydrolase-L1 in Glomerulonephritis
Subject Area
Nephrology
Term
from 2012 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 101885864
Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a key player of the ubiquitin system through the generation and stabilization of monomeric ubiquitin. Previously we were able to demonstrate in cell culture experiments, in vivo experiments and human glomerulopathies that UCH-L1 regulates the ubiquitin homeostasis in podocytes during glomerular disease. In a first part we want to analyse the exact functions of UCH-L1 in podocyte injury. Therefore, we generated podocyte selective UCH-L1 gene-deficient mice to induce an immunologic and a toxic model of podocyte damage and to subsequently assess clinical and morphological parameters of podocyte injury. Biochemical effects of UCH-L1 deficiency and mutations will be analysed in podocyte cell culture experiments. In a second part we will assess whether UCH-L1 expression in podocytes in human membranous nephropathy could serve as a prognostic factor for irreversible podocyte disease. This might help to gain insight into the possible pathologic role of UCH-L1 in the generation and progression of podocyte injury. In a third part we will analyse the role of UCH-L1 in immune mediated renal injury. Preliminary data demonstrate an UCH-L1 expression in murine kidney dendritic cells and an altered immune response in constitutive UCH-L1 mice treated with nephrotoxic serum. We will generate dendritic cell specific UCH-L1 deficient mice and analyse the immune response and clinical outcome in the model of nephrotoxic nephritis.
DFG Programme
Clinical Research Units
