%0 Journal Article
%T Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis
%A Carsten P Bramlage
%A Bj£¿rn Tampe
%A Michael Koziolek
%A Imad Maatouk
%A Jelena Bevanda
%A Peter Bramlage
%A Katharina Ahrens
%A Katharina Lange
%A Holger Schmid
%A Clemens D Cohen
%A Matthias Kretzler
%A Gerhard A M¨¹ller
%J BMC Nephrology
%D 2010
%I BioMed Central
%R 10.1186/1471-2369-11-31
%X 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-¦Â induced epithelial-to-mesenchymal transition (EMT), expression of TGF-¦Â receptor type I (TGF-¦ÂRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-¦Á induced apoptosis of proximal tubular cells.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-¦Á-induced apoptosis and TGF-¦Â-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-¦ÂRI. In addition, BMP-7 was able to reverse TGF-¦Â-induced phosphorylation of Smad 2.The findings suggest a protective role for BMP-7 by counteracting the TGF-¦Â and TNF-¦Á-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.Bone Morphogenetic Protein (BMP)-7 has been found to be renoprotective and to promote kidney regeneration in several animal models [1]. This finding was also observed in acute renal injury of the adult kidney as well as in chronic kidney disease [2-4]. The following mechanisms have been found to play a role in the effect of BMP-7: 1) regeneration of tubular epithelial cells by reversal of the epithelial-to
%U http://www.biomedcentral.com/1471-2369/11/31