Protease-activated receptors 1 and 3 drive epithelial-mesenchymal transition in pulmonary fibrosis

Rationale: Extravascular activation of the coagulation cascade in the lung is commonly observed in pulmonary fibrosis. Coagulation proteases exert profibrotic cellular effects via protease-activated receptors (PARs)-1 and -2. Objective: We investigated for the first time the potential role of two other members of the PAR family, namely PAR-3 and PAR-4, in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Results: Elevated expression of PAR-3, but not PAR-4, was detected in the lungs of IPF patients and bleomycin-challenged mice. Increased PAR-3 expression in fibrotic lungs was mainly attributable to alveo…