| dc.contributor.advisor | Gross, Oliver Prof. Dr. | |
| dc.contributor.author | Schütte, Peter | |
| dc.date.accessioned | 2014-05-09T07:44:12Z | |
| dc.date.available | 2014-05-27T22:50:04Z | |
| dc.date.issued | 2014-05-09 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0022-5EAA-2 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4490 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4490 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4490 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Der Einfluss des DDR1+/-/NPHS2+/R140Q-Genotyps auf die Interaktion zwischen glomerulärer Basalmembran und Schlitzmembran im Tiermodell | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | The Impact of the DDR1+/-/NPHS2+/R140Q-Genotype on the Interaction Between the Glomerular Basement Membrane and the Slit Diaphragm in an Animal Model | de |
| dc.contributor.referee | Gross, Oliver Prof. Dr. | |
| dc.date.examination | 2014-05-20 | |
| dc.description.abstracteng | Heterozygous Alport mutations of type IV collagen genes lead to Benign Familial Hematuria without excessive proteinruia or progression to end stage kidney disease. Heterozygous polymorphisms of the podocin-gene also do not cause significant impairment of renal function. However combinations of heterozygous Alport-mutations and heterozygous podocin polymorphisms cause proteinuria and in some cases end stage renal disease. This leads to the assumption of an interaction between the glomerular basement membrane and the slit diaphragm with the podocyte as the mediator. Impairment of this interaction could be of major importance in the development of glomerular disease. Therefore this paper adresses the mechanisms of this supposed interaction. In Alport syndrome the podocyte's contact with structures of the glomerular basement membrane is affected. Among others this contact is mediated by the collagen receptor DDR1. The animal model used in this paper featured a heterozygous DDR1-mutation as well as a heterozygous mutation of the podocin-gene NPHS2. Research concentrated on the impact of the DDR1+/-/NPHS2+/R140Q-genotype on glomerular and renal morphology and function. Electron microscopy showed changes of podocyte morphology in the sense of foot process dedifferenciation. In addition high and low molecular weight proteinuria was detectable in the bi-heterozygous animals. This negative impact of the DDR1+/-/NPHS2+/R140Q-genotype on podocyte differentiation and the integrity of the glomerular barrier suggest an important role of DDR1 and podocin in the postulated interaction between the glomerular basement membrane and the slit diaphragm. These phenotypic changes however did not cause chronic renal damage in the form of fibrosis or impairment of renal function: TGFß and CTGF as indicators of proinflammatory and profibrotic activity were not elevated in comparison to control animals. Likewise there was no increased accumulation of extracellulary matrix molecules in the sense of kidney fibrosis. Accordingly measurements of serum urea showed no impairment of global renal function in comparison to control animals. The results of this paper suggest that the interaction between the glomerular basement membrane and the slit diaphragm ist of great importance for the maintenance of glomerular function. In the future a more detailed understanding of these mechanisms of interaction could lead to the development of new therapeutic approaches in the management of glomerular diseases. | de |
| dc.contributor.coReferee | Wilting, Jörg Prof. Dr. | |
| dc.subject.eng | DDR1 | de |
| dc.subject.eng | Podocin | de |
| dc.subject.eng | Alport | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5EAA-2-1 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Medizin (PPN619874732) | de |
| dc.description.embargoed | 2014-05-27 | |
| dc.identifier.ppn | 785291822 | |