tailieunhanh - Báo cáo y học: "Bone Morphogenetic Protein (BMP)-4 and BMP-7 regulate differentially Transforming Growth Factor (TGF)-β1 in normal human lung fibroblasts (NHLF)"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: "Bone Morphogenetic Protein (BMP)-4 and BMP-7 regulate differentially Transforming Growth Factor (TGF)-β1 in normal human lung fibroblasts (NHLF). | Pegorier et al. Respiratory Research 2010 11 85 http content 11 1 85 RESPIRATORY RESEARCH RESEARCH Open Access Bone Morphogenetic Protein BMP -4 and BMP-7 regulate differentially Transforming Growth Factor TGF - 1 in normal human lung fibroblasts NHLF Sophie Pegorier Gaynor A Campbell A Barry Kay and Clare M Lloyd Abstract Background Airway remodelling is thought to be under the control of a complex group of molecules belonging to the Transforming Growth Factor TGF -superfamily. The Bone Morphogenetic Proteins BMPs belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-p-induced profibrotic functions in lung fibroblasts. Methods Cell cultures were exposed to TGF-pi alone or in the presence of BMP-4 or BMP-7 control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of 3H -thymidine. The expression of the mRNA encoding collagen type I and IV tenascin C and fibronectin in normal human lung fibroblasts NHLF was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of a-smooth muscle actin a-SMA by western blot and immunohistochemistry. The effect on matrix metalloproteinase MMP activity was assessed by zymography. Results We have demonstrated TGF-pi induced upregulation of mRNAs encoding the extracellular matrix proteins tenascin C fibronectin and collagen type I and IV when compared to unstimulated NHLF and confirmed these results at the protein level. BMP-4 but not BMP-7 reduced TGF-pi -induced extracellular matrix protein production. TGF-pi induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-pi-induced MMP-13 release compared to