%0 Journal Article %A Olivier Bardou %A Charlene Francois %A Nicolas Carlier %A Herve Mal %A Bruno Crestani %A Keren Borensztajn %T LSC 2014 abstract - Matriptase is an important player in fibroproliferative disorders %D 2014 %J European Respiratory Journal %P P3902 %V 44 %N Suppl 58 %X Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder which remains refractory to therapies. Recently, type II transmembrane serine proteases have emerged as key actors in pathophysiology, by proteolysis of cell surface receptors and/or cell environment, thereby orchestrating cell crosstalks. Among them, deregulation of the matriptase contributes to various proliferative disorders. These observations lead us to investigate the role of matriptase in pulmonary fibrosis.Matriptase expression and activity were analyzed in human lung material from controls and IPF patients. Human fibroblasts were stimulated with recombinant matriptase and the activation of key signaling pathways involved in IPF was analyzed. Impact of matriptase on human lung fibroblast proliferation and migration was then evaluated. Using the murine model of bleomycin-induced pulmonary fibrosis, mice were administrated for 14 days with 0 or 0.5mg of camostat mesilate (CM), a matriptase inhibitor. The markers of tissue fibrosis in lung homogenate were measured; cytokines and inflammatory cell influx in the bronchoalveolar lavage fluid (BALF) of the animals were assessed.We show that matriptase is upregulated in the lung and BALF of IPF patients compared to controls. In fibroblasts, matriptase induced the activation of p42/44, Akt, EGFR and Smad2/3 pathways. Finally, CM administration in bleomycin-treated mice led to a significant decrease of fibronectin and collagen expression. Cytokines and inflammatory cell influx in BALF were diminished in bleomycin+CM group compared to bleomycine-treated animals. Matriptase seems instrumental in pulmonary fibrosis, and targeting matriptase with CM could be a promising therapeutic way for IPF. %U