title: The role of bone morphogenetic protein-5 (BMP-5) in human nephrosclerosis.
abstract: BACKGROUND
  Bone morphogenetic protein-5 (BMP-5) has been shown to be essential for nephrogenesis. Its role in adult kidney and in patients with hypertensive nephrosclerosis is still unknown.
  
  
  METHODS
  BMP-5 expression was evaluated by immunostaining and real-time PCR in tissue samples from normal and nephrosclerotic human kidneys. The impact of transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α) and angiotensin-II (AT-II) on expression of BMP-5 and its receptors was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-5 were evaluated by testing its influence on TGF-ß-induced epithelial-to-mesenchymal transition (EMT), TNF-α-induced apoptosis of HK-2 cells and inflammatory cell infiltration.
  
  
  RESULTS
  BMP-5 expression was localized in tubular epithelial cells and significantly decreased in nephrosclerotic kidneys. Stimulation of HK-2 cells with TGF-ß, TNF-α and AT-II resulted in a significant decreased expression of BMP-5 and its receptors. BMP-5 attenuated TGF-ß-induced EMT, TNF-α-induced apoptosis and migration of mononuclear cells.
  
  
  CONCLUSIONS
  BMP-5 is expressed in the tubuli of adult kidneys. Its decreased expression in nephrosclerosis along with its regenerative capabilities in HK-2 cells may point to a protective role in hypertensive nephrosclerosis.
authors.affiliation: Department of Medicine, Nephrology and Rheumatology, Georg-August-University Göttingen, Robert-Koch Street 40, Göttingen, Germany. c.bramlage@med.uni-goettingen.de
authors.forename: Carsten P
authors.initials: CP
authors.lastname: Bramlage
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
authors.forename: Björn
authors.initials: B
authors.lastname: Tampe
authors.forename: Jelena
authors.initials: J
authors.lastname: Bevanda
authors.forename: Imad
authors.initials: I
authors.lastname: Maatouk
authors.forename: Michael
authors.initials: M
authors.lastname: Koziolek
authors.forename: Katharina
authors.initials: K
authors.lastname: Lange
authors.forename: Katharina
authors.initials: K
authors.lastname: Ahrens
authors.forename: Holger
authors.initials: H
authors.lastname: Schmid
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.forename: Peter
authors.initials: P
authors.lastname: Bramlage
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.forename: Frank
authors.initials: F
authors.lastname: Strutz
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000378:metabolism; D017209:Apoptosis; D001706:Biopsy; D055417:Bone Morphogenetic Protein 5 / Q000235:genetics / Q000378:metabolism*; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009400:Nephrosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C525814:BMP5 protein, human; D055417:Bone Morphogenetic Protein 5; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D052004:Bone Morphogenetic Protein Receptors