Effekte von Calcitriol auf die renale Fibrogenese

Volland, Marcel

dc.contributor.advisor	Strutz, Frank Prof. Dr.	de
dc.contributor.author	Volland, Marcel	de
dc.date.accessioned	2013-01-14T15:17:32Z	de
dc.date.available	2013-01-30T23:50:52Z	de
dc.date.issued	2012-05-11	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-000D-EFAC-E	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-1517
dc.description.abstract	Immer mehr Patienten sind von progressiven Nierenerkrankungen betroffen und daher ist die Etablierung einer innovativen Therapiestrategie von gro	de
dc.format.mimetype	application/pdf	de
dc.language.iso	ger	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	de
dc.title	Effekte von Calcitriol auf die renale Fibrogenese	de
dc.type	doctoralThesis	de
dc.title.translated	Effects of calcitriol on the process of renal fibrogenesis	de
dc.contributor.referee	Strutz, Frank Prof. Dr.	de
dc.date.examination	2012-05-30	de
dc.subject.dnb	610 Medizin, Gesundheit	de
dc.subject.gok	MED 418	de
dc.subject.gok	MED 419	de
dc.description.abstracteng	Calcitriol 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.coReferee	Jarry, Hubertus Prof. Dr.	de
dc.subject.topic	Medicine	de
dc.subject.ger	Renale Fibrose	de
dc.subject.ger	Calcitriol	de
dc.subject.ger	Fibroblasten	de
dc.subject.ger	EMT	de
dc.subject.ger	Kollagen Typ I	de
dc.subject.ger	Fibronektin	de
dc.subject.ger	E-Cadherin	de
dc.subject.ger	Tk173	de
dc.subject.ger	Tk188	de
dc.subject.ger	HK-2	de
dc.subject.eng	renal fibrosis	de
dc.subject.eng	calcitriol	de
dc.subject.eng	fibroblasts	de
dc.subject.eng	EMT	de
dc.subject.eng	collagen	de
dc.subject.eng	fibronectin	de
dc.subject.eng	Ecadherin	de
dc.subject.eng	Tk173	de
dc.subject.eng	Tk188	de
dc.subject.eng	HK-2	de
dc.subject.bk	44.61	de
dc.subject.bk	44.88	de
dc.subject.bk	44.89	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-3500-6	de
dc.identifier.purl	webdoc-3500	de
dc.affiliation.institute	Medizinische Fakultät	de
dc.identifier.ppn	72052492X	de

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