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Effects And Mechanisms Of Bone Morphogenetic Protein-7 On Epithelial-Mesenchymal Transition (EMT) Of Renal Tubular Cells

Posted on:2005-09-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:X Y TanFull Text:PDF
GTID:1104360185473731Subject:Scientific kidney disease
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BackgroundEpithelial- Mesenchymal transition (EMT) of renal tubular cells has been proved to be one of the major mechanisms that underlie the renal tubular-interstitial fibrosis. In addition, the key role of transforming growth factor- β 1 (TGF- β 1) in transdifferentiation has been recognized for a few years, while monocyte chemoattractant protein-l(MCP-l), the potent chemoattractant cytokine for the modulating infiltration of monocyte/macrophage in renal interstitium, also has a possible role as a synergistic factor participating in the EMT process induced with aristolochic acid. More recent studies have documented the protective effects of bone morphogenetic protein-7 (BMP-7) on acute and chronic impairment of renal function and progress of renal pathological lesions in various animal models. Several researches also showed that BMP-7 might ameliorate and even reverse the process of EMT. Our study was to further elucidate changes of MCP-1 and TGF- β1 expressions in the process of BMP-7 acting on the EMT, so as to understand the mechanism of renoprotective effects of BMP-7. Leflunomide, a novel immuno-suppressive drug, has been applied in the treatment of various renal diseases. In our study, we also observe effects of this drug on renal interstitial fibrosis and EMT.Aims1. To examine the effect of BMP-7 on EMT induced with TGF-β1 when the renal tubular epithelium was pre-treated with BMP-7 or concomitantly treated with TGF-β1 and BMP-7.2. To test the change of TGF- β 1 expression and Smad 3 expression in MCP-1 induced EMT process and the effect of BMP-7 on EMT mentioned above.
Keywords/Search Tags:Bone morphogenetic protein-7, Transforming growth factor-β1, Leflunomide, Smad 3, renal interstitial fibrosis, Unilateral ureteral obstruction, Monocyte chemoattractant protein-1, Epithelial-mesenchymal transdifferentiation
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