Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis
dc.contributor.author | Bramlage, Carsten P | |
dc.contributor.author | Tampe, Björn | |
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 | Müller, Gerhard A | |
dc.date.accessioned | 2015-08-07T17:36:42Z | |
dc.date.available | 2015-08-07T17:36:42Z | |
dc.date.issued | 2010-11-16 | |
dc.identifier.citation | BMC Nephrology. 2010 Nov 16;11(1):31 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/112615 | en_US |
dc.description.abstract | 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-β induced epithelial-to-mesenchymal transition (EMT), expression of TGF-β receptor type I (TGF-βRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-α 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-α-induced apoptosis and TGF-β-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-βRI. In addition, BMP-7 was able to reverse TGF-β-induced phosphorylation of Smad 2. Conclusions The findings suggest a protective role for BMP-7 by counteracting the TGF-β and TNF-α-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.title | Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis | |
dc.type | Article | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/112615/1/12882_2010_Article_182.pdf | |
dc.identifier.doi | 10.1186/1471-2369-11-31 | en_US |
dc.language.rfc3066 | en | |
dc.rights.holder | Bramlage et al. | |
dc.date.updated | 2015-08-07T17:36:43Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.