title: Targeting coagulation factor receptors - protease-activated receptors in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with a 5-year mortality rate of > 50% and unknown etiology. Treatment options remain limited and, currently, only two drugs are available, i.e. nintedanib and pirfenidone. However, both of these antifibrotic agents only slow down the progression of the disease, and do not remarkably prolong the survival of IPF patients. Hence, the discovery of new therapeutic targets for IPF is crucial. Studies exploring the mechanisms that are involved in IPF have identified several possible targets for therapeutic interventions. Among these, blood coagulation factor receptors, i.e. protease-activated receptors (PARs), are key candidates, as these receptors mediate the cellular effects of coagulation factors and play central roles in influencing inflammatory and fibrotic responses. In this review, we will focus on the controversial role of the coagulation cascade in the pathogenesis of IPF. In the light of novel data, we will attempt to reconciliate the apparently conflicting data and discuss the possibility of pharmacologic targeting of PARs for the treatment of fibroproliferative diseases.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.|Inserm UMR1152, Medical School Xavier Bichat, Paris, France.|Département Hospitalo-universtaire FIRE (Fibrosis, Inflammation and Remodeling) and LabEx Inflamex, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Borensztajn
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: Spek
mesh_terms: D000818:Animals; D000925:Anticoagulants; D001761:Bleomycin / Q000737:chemistry; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000401:mortality; D007249:Inflammation; D007783:Lactones / Q000627:therapeutic use; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors; D044462:Receptors, Proteinase-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D044464:Receptor, PAR-2; D044462:Receptors, Proteinase-Activated; D001761:Bleomycin; C530299:vorapaxar
keywords: anticoagulants; fibrosis; idiopathic pulmonary fibrosis; receptor, PAR-1; receptor, PAR-2; receptors, proteinase-activated