TY - T1的组织蛋白酶S减少cy的目标stic fibrosis-like lung disease JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01523-2018 VL - 53 IS - 3 SP - 1801523 AU - Small, Donna M. AU - Brown, Ryan R. AU - Doherty, Declan F. AU - Abladey, Anthony AU - Zhou-Suckow, Zhe AU - Delaney, Rebecca J. AU - Kerrigan, Lauren AU - Dougan, Caoifa M. AU - Borensztajn, Keren S. AU - Holsinger, Leslie AU - Booth, Robert AU - Scott, Christopher J. AU - López-Campos, Guillermo AU - Elborn, J. Stuart AU - Mall, Marcus A. AU - Weldon, Sinéad AU - Taggart, Clifford C. Y1 - 2019/03/01 UR - //www.qdcxjkg.com/content/53/3/1801523.abstract N2 - Cathepsin S (CatS) is upregulated in the lungs of patients with cystic fibrosis (CF). However, its role in CF lung disease pathogenesis remains unclear.In this study, β-epithelial Na+ channel-overexpressing transgenic (βENaC-Tg) mice, a model of CF-like lung disease, were crossed with CatS null (CatS−/−) mice or treated with the CatS inhibitor VBY-999.Levels of active CatS were elevated in the lungs of βENaC-Tg mice compared with wild-type (WT) littermates. CatS−/−βENaC-Tg mice exhibited decreased pulmonary inflammation, mucus obstruction and structural lung damage compared with βENaC-Tg mice. Pharmacological inhibition of CatS resulted in a significant decrease in pulmonary inflammation, lung damage and mucus plugging in the lungs of βENaC-Tg mice. In addition, instillation of CatS into the lungs of WT mice resulted in inflammation, lung remodelling and upregulation of mucin expression. Inhibition of the CatS target, protease-activated receptor 2 (PAR2), in βENaC-Tg mice resulted in a reduction in airway inflammation and mucin expression, indicating a role for this receptor in CatS-induced lung pathology.Our data indicate an important role for CatS in the pathogenesis of CF-like lung disease mediated in part by PAR2 and highlight CatS as a therapeutic target.Cathepsin S is involved in inflammation, mucus production and lung tissue damage in a model of CF-like lung disease http://ow.ly/tHcm30nhlcX ER -