tailieunhanh - Báo cáo y học: " Effects of PPARg ligands on TGF-b1-induced epithelial-mesenchymal transition in alveolar epithelial cells"

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:Effects of PPARg ligands on TGF-b1-induced epithelial-mesenchymal transition in alveolar epithelial cells. | Tan et al. Respiratory Research 2010 11 21 http content 11 1 21 RESPIRATORY RESEARCH RESEARCH Open Access Effects of PPARg ligands on TGF-p1-induced epithelial-mesenchymal transition in alveolar epithelial cells Xiahui Tan1 2 Hayat Dagher1 Craig A Hutton2 Jane E Bourke1 Abstract Background Transforming growth factor p1 TGF-p1 -mediated epithelial mesenchymal transition EMT of alveolar epithelial cells AEC may contribute to lung fibrosis. Since PPARg ligands have been shown to inhibit fibroblast activation by TGF-b1 we assessed the ability of the thiazolidinediones rosiglitazone RGZ and ciglitazone CGZ to regulate TGF-p1-mediated EMT of A549 cells assessing changes in cell morphology and expression of cell adhesion molecules E-cadherin epithelial cell marker and N-cadherin mesenchymal cell marker and collagen 1a1 COL1A1 CTGF and MMP-2 mRNA. Methods Serum-deprived A549 cells human AEC cell line were pre-incubated with RGZ and CGZ 1 - 30 gM in the absence or presence of the PPARg antagonist GW9662 10 gM before TGFp-1 ng ml treatment for up to 72 hrs. Changes in E-cadherin N-cadherin and phosphorylated Smad2 and Smad3 levels were analysed by Western blot and changes in mRNA levels including COL1A1 assessed by RT-PCR. Results TGFp-1 ng ml -induced reductions in E-cadherin expression were associated with a loss of epithelial morphology and cell-cell contact. Concomitant increases in N-cadherin MMP-2 CTGF and COL1A1 were evident in predominantly elongated fibroblast-like cells. Neither RGZ nor CGZ prevented TGFp1-induced changes in cell morphology and PPARg-dependent inhibitory effects of both ligands on changes in E-cadherin were only evident at submaximal TGF-p1 ng ml . However both RGZ and CGZ inhibited the marked elevation of N-cadherin and COL1A1 induced by TGF-p1 ng ml with effects on COL1A1 prevented by GW9662. Phosphorylation of Smad2 and Smad3 by TGF-p1 was not inhibited by RGZ or CGZ. Conclusions RGZ and CGZ .