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: " The effect of cathepsin K deficiency on airway development and TGF-b1 degradation. | Zhang et al. Respiratory Research 2011 12 72 http content 12 1 72 RESPIRATORY RESEARCH RESEARCH Open Access The effect of cathepsin K deficiency on airway development and TGF-P1 degradation Dongwei Zhang1 Nelson Leung1 Ekkehard Weber2 Paul Saftig3 and Dieter Bromme1 Background Cathepsin K a cysteine protease predominantly expressed in osteoclasts is a major drug target for the treatment of osteoporosis. Recent findings however indicate that cathepsin K is also involved in non-skeletal metabolism. The development of fibrotic phenotypes in lung and skin is a concern for cathepsin K inhibitors presently evaluated in clinical trials. Cathepsin K is expressed in lung tissue and has been implicated in lung fibrosis. However little is known about the role of cathepsin K in airway development and its effect on TGF-b1 degradation. Methods We investigated the effects of cathepsin K-deficiency on alterations in airway integrity extracellular matrix composition and TGF-b1 expression and degradation. Lung homogenates of wild-type and cathepsin K-deficient mice were used to evaluate their contents of collagen glycosaminoglycans and TGF-P1. The accessibility of TGF-p1 to cathepsin K-mediated degradation was determined in vitro and lung fibroblast proliferations in wildtype and cathepsin K-deficient cells were evaluated. Results Lung airway cathepsin K expression in wild-type mice remained constant between 1 and 6 months of age and the airway integrity was maintained. In contrast after 2 months of age all Ctsk- mice demonstrated increased airway epithelium thickness by 16-28 a lower structural airway integrity 1-2 score units lower elevated cytokeratin expression of 12 increased a-actin and vimentin expression by 50 and 70 increased area of smooth muscle cells by 15 elevated hydroxyproline and GAGs content by 20 and 25 and increased TGF-b1 expression by 25 . TGF-b1 proved an efficient substrate of cathepsin K and TGF-b1 protein content in lung was .
