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Funktionelle Analyse der Discoidin Domäne Rezeptoren während der Nierenentwicklung und der Pathogenese des Nierenversagens
Antragsteller
Dr. Wolfgang Vogel (†)
Fachliche Zuordnung
Dermatologie
Förderung
Förderung von 2000 bis 2003
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5250538
Discoidin Domain Receptors are widely expressed through human and mouse tissues. Whereas the tyrosine kinase function of DDR1 is activated by basement membrane and fibrillar collagens, DDR2 is activated by fibrillar collagens only. By in situ staining, DDR1 expression is seen in the developing mouse kidney as well as in the distal tubules of human adult kidney. DDR2 expression in the kidney was detected using Northern hybridisation. The project will study DDR function in normal and diseased kidney by analysing the expression of receptors and their cognate ligands at the cellular level using immunohistochemical methods. Human renal biopsy tissue will be used to analyse alterations in DDR expression during the progression of renal disease. Since reduced DDR2 signaling with deglycosylated collagen and enhanced activation of DDR by in vitro glycated collagen has been reported, we will focus on samples taken from patients with diabetic nephropathy. The project will utilise microarray technology to elucidate DDR target genes in primary human kidney cells as well as in mouse kidney cells that have been derived from DDR1 and DDR2 knock out animals.
DFG-Verfahren
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