The role of bone morphogenetic protein-5 (BMP-5) in human nephrosclerosis

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-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha) 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-beta-induced epithelial-to-mesenchymal transition (EMT), TNF-alpha-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-beta, TNF-alpha and AT-II resulted in a significant decreased expression of BMP-5 and its receptors. BMP-5 attenuated TGF-beta-induced EMT, TNF-alpha-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.