tailieunhanh - Báo cáo y học: " Phosphodiesterase 6 subunits are expressed and altered in idiopathic pulmonary fibrosis"

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: Phosphodiesterase 6 subunits are expressed and altered in idiopathic pulmonary fibrosis. | Nikolova et al. Respiratory Research 2010 11 146 http content 11 1 146 RESPIRATORY RESEARCH RESEARCH Open Access Phosphodiesterase 6 subunits are expressed and altered in idiopathic pulmonary fibrosis Sevdalina Nikolova1 Andreas Guenther1 2 Rajkumar Savai1 Norbert Weissmann1 Hossein A Ghofrani1 KAol 2 n io fnn in c hoff3 Ol i or Rin bo I horn3 A a I for Id lonofbn4 Rm Korf nc A i nebo 11 5 A omor Roon or1 5 Meiailie Konigso Oiivei Eici e eig vvaitei Kiepeti o Roeit Vosvviiici e Weinei Seegei Friedrich Grimminger1 Ralph T Schermuly1 5 Soni S Pullamsetti1 5 Abstract Background Idiopathic Pulmonary Fibrosis IPF is an unresolved clinical issue. Phosphodiesterases PDEs are known therapeutic targets for various proliferative lung diseases. Lung PDE6 expression and function has received little or no attention. The present study aimed to characterize i PDE6 subunits expression in human lung ii PDE6 subunits expression and alteration in IPF and iii functionality of the specific PDE6D subunit in alveolar epithelial cells AECs . Methodology Principal Findings PDE6 subunits expression in transplant donor n 6 and IPF n 6 lungs was demonstrated by real-time quantitative q RT-PCR and immunoblotting analysis. PDE6D mRNA and protein levels and PDE6G H protein levels were significantly down-regulated in the IPF lungs. Immunohistochemical analysis showed alveolar epithelial localization of the PDE6 subunits. This was confirmed by qRT-PCR from human primary alveolar type AT II cells demonstrating the down-regulation pattern of PDE6D in IPF-derived ATII cells. In vitro PDE6D protein depletion was provoked by transforming growth factor TGF -p1 in A549 AECs. PDE6D siRNA-mediated knockdown and an ectopic expression of PDE6D modified the proliferation rate of A549 AECs. These effects were mediated by increased intracellular cGvP levels and decreased ERK phosphorylation. Conclusions Significance Collectively we report previously unrecognized PDE6 expression in human