title: BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition in human renal proximal tubular epithelial cells.
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.
authors: Department of Nephrology, The First Affiliated Hospital, Fujian Medical University, Fuzhou - PR China.
authors: Yanfang
authors: Y
authors: Xu
authors: Jianxin
authors: J
authors: Wan
authors: Dewen
authors: D
authors: Jiang
authors: Xiaonan
authors: X
authors: Wu
mesh_terms: D000199:Actins / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D004847:Epithelial Cells / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D008648:Mesoderm / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D055419:Bone Morphogenetic Protein 7; C526317:CCN2 protein, human; D015820:Cadherins; D024042:Collagen Type I; D005353:Fibronectins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor