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Effekte von Calcitriol auf die renale Fibrogenese

dc.contributor.advisorStrutz, Frank Prof. Dr.de
dc.contributor.authorVolland, Marcelde
dc.date.accessioned2013-01-14T15:17:32Zde
dc.date.available2013-01-30T23:50:52Zde
dc.date.issued2012-05-11de
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-000D-EFAC-Ede
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-1517
dc.description.abstractImmer mehr Patienten sind von progressiven Nierenerkrankungen betroffen und daher ist die Etablierung einer innovativen Therapiestrategie von grode
dc.format.mimetypeapplication/pdfde
dc.language.isogerde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/de
dc.titleEffekte von Calcitriol auf die renale Fibrogenesede
dc.typedoctoralThesisde
dc.title.translatedEffects of calcitriol on the process of renal fibrogenesisde
dc.contributor.refereeStrutz, Frank Prof. Dr.de
dc.date.examination2012-05-30de
dc.subject.dnb610 Medizin, Gesundheitde
dc.subject.gokMED 418de
dc.subject.gokMED 419de
dc.description.abstractengCalcitriol may decrease extracellular matrix accumulation in animal models of progressive kidney disease. The mechanisms are only partially understood. In order to understand the antifibrotic effects of calcitriol, we analyzed the effects of calcitriol on human renal fibroblasts (Tk173 and Tk188) and proximal tubular epithelial cells (HK-2) in vitro in regard to matrix synthesis (expression of collagen type I and fibronectin), matrix degradation (MMP-2 and MMP-9), activation of fibroblasts to myofibroblasts (de novo synthesis of alpha-sm-actin) and cell proliferation. Moreover, key aspects of epithelial-mesenchymal-transition (EMT) were studied by expression analyses of several epithelial (E-Cadherin, ZO-1) and mesenchymal marker proteins (Vimentin, S100A4, alpha-sm-actin). In fibroblasts, calcitriol induced a reduction of the TGF-β induced collagen synthesis of 52.45 ± 12.23 per cent (Tk173, p=0.0006). Furthermore, there was an effect on EMT in tubular epithelial cells by inhibiting TGF-βinduced downregulation of E-Cadherin (upregulation of 44.9 ± 19.6 per cent, p=0.0354). However, there was no major effect on the mesenchymal marker proteins vimentin, S100A4 and alpha-sm-actin. In matrixdegradation calcitriol induced synthesis of MMP-9 compared to TGF-β stimulated cells of 38.56 ± 22.14 per cent (p=0.2776). Finally, calcitriol inhibited proliferation in fibroblasts by 51.5 ± 8.62 per cent (Tk173, p=0.0003) and 43.49 ± 4.13 per cent (Tk188, p<0.0001) after 48 hrs. In tubular epithelial cells, it decreased proliferation by 57.17 ± 11.07 per cent after 48 hrs (p=0.0004). Calcitriol did reduce matrix synthesis in fibroblasts and tubular epithelial cells albeit to only a moderate degree in the latter. It reduced fibroblast and tubular epithelial cell number and inhibited TGF-β1driven EMT. These studies provide in vitro explanations for many effects of calcitriol found in animal studies.de
dc.contributor.coRefereeJarry, Hubertus Prof. Dr.de
dc.subject.topicMedicinede
dc.subject.gerRenale Fibrosede
dc.subject.gerCalcitriolde
dc.subject.gerFibroblastende
dc.subject.gerEMTde
dc.subject.gerKollagen Typ Ide
dc.subject.gerFibronektinde
dc.subject.gerE-Cadherinde
dc.subject.gerTk173de
dc.subject.gerTk188de
dc.subject.gerHK-2de
dc.subject.engrenal fibrosisde
dc.subject.engcalcitriolde
dc.subject.engfibroblastsde
dc.subject.engEMTde
dc.subject.engcollagende
dc.subject.engfibronectinde
dc.subject.engEcadherinde
dc.subject.engTk173de
dc.subject.engTk188de
dc.subject.engHK-2de
dc.subject.bk44.61de
dc.subject.bk44.88de
dc.subject.bk44.89de
dc.identifier.urnurn:nbn:de:gbv:7-webdoc-3500-6de
dc.identifier.purlwebdoc-3500de
dc.affiliation.instituteMedizinische Fakultätde
dc.identifier.ppn72052492Xde


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