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  • 2010Journal Article
    [["dc.bibliographiccitation.artnumber","31"],["dc.bibliographiccitation.journal","BMC Nephrology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Bramlage, Carsten Paul"],["dc.contributor.author","Tampe, Bjoern"],["dc.contributor.author","Koziolek, Michael"],["dc.contributor.author","Maatouk, Imad"],["dc.contributor.author","Bevanda, Jelena"],["dc.contributor.author","Bramlage, Peter"],["dc.contributor.author","Ahrens, Katharina"],["dc.contributor.author","Lange, Katharina"],["dc.contributor.author","Schmid, Holger"],["dc.contributor.author","Cohen, Clemens D."],["dc.contributor.author","Kretzler, Matthias"],["dc.contributor.author","Mueller, Georg Anton"],["dc.date.accessioned","2018-11-07T08:36:49Z"],["dc.date.available","2018-11-07T08:36:49Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods: BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-beta induced epithelial-to-mesenchymal transition (EMT), expression of TGF-beta receptor type I (TGF-beta RI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-alpha induced apoptosis of proximal tubular cells. Results: BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-alpha-induced apoptosis and TGF-beta-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-beta RI. In addition, BMP-7 was able to reverse TGF-beta-induced phosphorylation of Smad 2. Conclusions: The findings suggest a protective role for BMP-7 by counteracting the TGF-beta and TNF-alpha-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease."],["dc.identifier.doi","10.1186/1471-2369-11-31"],["dc.identifier.isi","000208334700001"],["dc.identifier.pmid","21080950"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5802"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18396"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2369"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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