Platelet-Derived Growth Factor (PDGF)-C/PDGF-receptor-alpha-interaction during acute kidney damage and renal regeneration

• Applicant: Professor Dr. Tammo Ostendorf
• Subject Area: Nephrology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 397463556

Acute kidney damage occurs very frequently and has serious consequences for the affected patients and the healthcare systems. Acute kidney damage is particularly characterized by renal epithelial and endothelial damage, as occurs in the tubulointerstitium in acute renal failure and in glomeruli in rapid progressive glomerulonephritis. However, following mild to moderate acute renal damage, there is also an initiation of programs which lead to cellular repair with tissue regeneration and resolution of inflammatory processes. The latter processes can result in restored normal renal function or nearly normal renal function in the affected patients. Such successful regeneration processes become increasingly unlikely in case of extensive and/or chronic renal damage. With regard to therapeutic interventions in acute renal damage, more detailed knowledge on the processes involved is necessary, which on the one hand lead to progressive renal damage in the acute phase, and on the other initiate cellular regeneration processes. Substantial preliminary work led us to the hypothesis, that PDGF-C/PDGFR-alpha-interactions have an important function for the vascular tone, as well as for induction and regeneration of acute epithelial and endothelial damage in the kidney. In the present project, we aim to check this hypothesis in three work packages. Detailed knowledge thereof could provide important information for new therapies in acute renal diseases, but also safety-relevant knowledge, e.g. for the use of PDGF-C antagonists in renal fibrosis.In the present project we plan to analyse the role of PDGF-C/PDGFR-alpha-interaction a) for the vascular tone in hypertension-associated renal damage, b) for the damage and regeneration of tubular cells in acute renal failure, and c) for acute glomerular damage and regeneration in crescentic glomerulonephritis. To this aim, several newly established mouse lines with genetically constitutive, but especially also conditional, cell-specific deficiency of PDGF-C and PDGFR-alpha will be applied in relevant models of acute renal damage. Finally, data from these genetic models will be complemented and checked by the usage of effective and specific PDGF-C antagonists.

• DFG Programme: Research Grants