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:" Simvastatin inhibits TGFb1-induced fibronectin in human airway fibroblasts. | Schaafsma et al. Respiratory Research 2011 12 113 http content 12 1 113 RESPIRATORY RESEARCH RESEARCH Open Access Simvastatin inhibits TGFp1-induced fibronectin in human airway fibroblasts Dedmer Schaafsma1 2 3 Karol D McNeill1 2 Mark M Mutawe1 2 Saeid Ghavami1 2 4 Helmut Unruh5 Eric Jacques6 Michel Laviolette6 Jamila Chakir6 and Andrew J Halayko1 2 3 4 Abstract Background Bronchial fibroblasts contribute to airway remodelling including airway wall fibrosis. Transforming growth factor TGF -p1 plays a major role in this process. We previously revealed the importance of the mevalonate cascade in the fibrotic response of human airway smooth muscle cells. We now investigate mevalonate cascade-associated signaling in TGFp1-induced fibronectin expression by bronchial fibroblasts from non-asthmatic and asthmatic subjects. Methods We used simvastatin 1-15 qM to inhibit 3-hydroxy-3-methlyglutaryl-coenzyme A HMG-CoA reductase which converts HMG-CoA to mevalonate. Selective inhibitors of geranylgeranyl transferase-1 GGT1 GGTI-286 10 qM and farnesyl transferase FT FTI-277 10 qM were used to determine whether GGT1 and FT contribute to TGFb1-induced fibronectin expression. In addition we studied the effects of co-incubation with simvastatin and mevalonate 1 mM geranylgeranylpyrophosphate 30 qM or farnesylpyrophosphate 30 qM . Results Immunoblotting revealed concentration-dependent simvastatin inhibition ofTGFp1 ng ml 48 h -induced fibronectin. This was prevented by exogenous mevalonate or isoprenoids geranylgeranylpyrophosphate or farnesylpyrophosphate . The effects of simvastatin were mimicked by GGTI-286 but not FTI-277 suggesting fundamental involvement of GGT1 in TGFp1-induced signaling. Asthmatic fibroblasts exhibited greater TGFp1-induced fibronectin expression compared to non-asthmatic cells this enhanced response was effectively reduced by simvastatin. Conclusions We conclude that TGFp1-induced fibronectin expression in airway fibroblasts .
