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  • Title: BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition in human renal proximal tubular epithelial cells.
    Author: Xu Y, Wan J, Jiang D, Wu X.
    Journal: J Nephrol; 2009; 22(3):403-10. PubMed ID: 19557718.
    Abstract:
    BACKGROUND: A large proportion of interstitial fibroblasts actually originate from tubular epithelial cells via the epithelial-to-mesenchymal transition (EMT) in renal fibrogenesis. Transforming growth factor-beta1 (TGF-beta1) is capable of initiating and completing the entire EMT course. Bone morphogenetic protein-7 (BMP-7) is a member of the TGF-beta superfamily. Recent studies indicate that BMP-7 could reverse established renal fibrosis in mice, primarily through counteracting TGF-beta1-mediated EMT. Therefore, we tested the hypothesis that BMP-7 functions by antagonizing profibrogenic events that are induced by TGF-beta1 in cultured human renal proximal tubular epithelial (HK-2) cells. METHODS: Cultured HK-2 cells were treated with TGF-beta1 (3 ng/mL) or a combination of TGF-beta1 and BMP-7 (100-400 ng/mL) for 48 hours. Morphological changes were assessed by phase contrast microscopy. The expression of alpha-smooth muscle actin (alpha-SMA), E-cadherin, fibronectin, collagen I and connective tissue growth factor (CTGF) was analyzed by immunofluorescence, reverse transcriptase polymerase chain reaction and Western blotting. RESULTS: Incubation of HK-2 cells with 3 ng/mL TGF-beta1 for 48 hours induced EMT, in association with decreased E-cadherin expression, increased alpha-SMA, fibronectin, collagen I and CTGF expression, and loss of epithelial morphology. BMP-7 inhibited all these effects in a dose-dependent manner. In addition, 200 ng/mL BMP-7 reversed TGF-beta1-induced EMT, in association with reexpression of endogenous E-cadherin. CONCLUSIONS: These data suggest that BMP-7 attenuates progressive loss of kidney function and renal fibrosis through counteracting TGF-beta1-mediated EMT.
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