Cathepsin S plays crucial in chronic lung disorders

May 8, 2019 0 By FM

Donna M. Small et al unveiled the importance of enzyme cathepsin S (CatS) in the pathogenesis of chronic lung diseases like cystic fibrosis (CF), highlighting its role as a therapeutic target. CatS is seen to be upregulated in the lungs of patients with cystic fibrosis. The study used transgenic mice models expressing CF-like lung disease and were crossed with cathepsin S null control mice or treated with CatS inhibitor. Levels of active CatS were elevated in lungs of the CF mice model compared to the control mice. The crossed mice progeny exhibited decreased pulmonary inflammation, mucous obstruction and lung damage compared to the CF mice models. Pharmacological inhibition of CatS revealed a significant decrease in inflammation and damage to the lungs. Instillation of the enzyme into lungs of control mice resulted in an upregulation of mucin expression. Inhibition of CatS target, protease-activated receptor-2 (PAR-2) also resulted in a decreased airway inflammation and mucin expression establishing the role of the receptor in CatS-induced lung pathology. The study thus demonstrates the significant role of CatS as a potential drug target in treating chronic lung disorders.

Source: European Respiratory Journal 2019; DOI: 10.1183/13993003.01523-2018 https://erj.ersjournals.com/content/early/2019/01/02/13993003.01523-2018