title: Bone morphogenetic protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis.
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.
authors.affiliation: Department of Medicine, Nephrology and Rheumatology, Georg-August-University Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. c.bramlage@med.uni-goettingen.de
authors.forename: Carsten P
authors.initials: CP
authors.lastname: Bramlage
authors.forename: Björn
authors.initials: B
authors.lastname: Tampe
authors.forename: Michael
authors.initials: M
authors.lastname: Koziolek
authors.forename: Imad
authors.initials: I
authors.lastname: Maatouk
authors.forename: Jelena
authors.initials: J
authors.lastname: Bevanda
authors.forename: Peter
authors.initials: P
authors.lastname: Bramlage
authors.forename: Katharina
authors.initials: K
authors.lastname: Ahrens
authors.forename: Katharina
authors.initials: K
authors.lastname: Lange
authors.forename: Holger
authors.initials: H
authors.lastname: Schmid
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
mesh_terms: D000368:Aged; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009400:Nephrosclerosis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D012333:RNA, Messenger