Antagonistic effect of bone morphogenetic protein-7 on transforming growth factor-β1 induced extracellular matrix synthesis
Nan Chen
Abstract
Nan Chen
Abstract
Objective:To investigate the molecular details in antifibrotic effects of bone morphogenetic protein-7(BMP-7)on TGF-β1induced extra-cellular matrix(ECM)production.Methodology:In human proximal tubular cells(HK-2),the expressions of fibronectin,collagen type III and collagen type I were measured by real-time PCR and western blot.The expressions of Smads were examined by Western blot and NK-B activity was detected by electrophoretic mobility shift assay(EMSA).Results:BMP-7 could antagonized TGF-β1 induced collagen type I,collagen type III and fibronectin mRNA and protein expression in a dose-dependent manner.The application of BMP-7 in the presence of TGF-β1 resulted in reduced Smad 2/3 phosphorylation.BMP-7 could also significantly down-regulated TGF-β1 induced NF-κB activity.Conclusion:BMP-7 could counteract TGF-β1 induced fibrogenesis.The inhibitory effects of BMP-7 on TGF-β1 induced ECM production could be mediated by inhibiting Smad 2/3 phosphorylation and NF-κB activity.
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Objective:To investigate the molecular details in antifibrotic effects of bone morphogenetic protein-7(BMP-7)on TGF-β1induced extra-cellular matrix(ECM)production.Methodology:In human proximal tubular cells(HK-2),the expressions of fibronectin,collagen type III and collagen type I were measured by real-time PCR and western blot.The expressions of Smads were examined by Western blot and NK-B activity was detected by electrophoretic mobility shift assay(EMSA).Results:BMP-7 could antagonized TGF-β1 induced collagen type I,collagen type III and fibronectin mRNA and protein expression in a dose-dependent manner.The application of BMP-7 in the presence of TGF-β1 resulted in reduced Smad 2/3 phosphorylation.BMP-7 could also significantly down-regulated TGF-β1 induced NF-κB activity.Conclusion:BMP-7 could counteract TGF-β1 induced fibrogenesis.The inhibitory effects of BMP-7 on TGF-β1 induced ECM production could be mediated by inhibiting Smad 2/3 phosphorylation and NF-κB activity.
Key concepts: SMAD, Fibronectin, Extracellular matrix, Western blot, Bone morphogenetic protein 2, Bone morphogenetic protein 7, Bone morphogenetic protein, Transforming growth factor