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The role of bone morphogenetic protein-5 (BMP-5) in human nephrosclerosis
Carsten P Bramlage1, Gerhard A Müller, Björn Tampe
1Department of Medicine, Nephrology and Rheumatology, Georg-August-University Göttingen, Robert-Koch Street 40, Göttingen, Germany. c.bramlage@med.uni-goettingen.de
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.
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