Thrombin stimulates the expression of PDGF in lung epithelial cells

Several growth factors, including platelet-derived growth factor (PDGF), ha ve been implicated in the mechanism of lung and airway remodeling. In the p resent study, we evaluated whether thrombin may promote lung and airway rem odeling by increasing PDGF production from lung and airway epithelial cells . Conditioned medium (CM) was prepared by treating epithelial cells with in creasing concentrations of thrombin; before use in the assays, CM was treat ed with hirudin until complete inhibition of thrombin activity. CM from epi thelial cells stimulated the proliferation of lung fibroblasts and bronchia l smooth muscle cells. Anti-PDGF antibody significantly inhibited this CM p roliferative activity, implicating PDGF in this effect. Enzyme immunoassay and RT-PCR demonstrated that thrombin induced the secretion and expression of PDGF from bronchial and alveolar epithelial cells. RT-PCR showed that ep ithelial cells express the thrombin receptors protease-activated receptor ( PAR)-1, PAR-3, and PAR-4. The PAR-1 agonist peptide was also found to induc e PDGF secretion from epithelial cells, suggesting that the cellular effect of thrombin occurs via a PAR-1-mediated mechanism. Overall, this study sho wed for the first time that thrombin may play an important role in the proc ess of lung and airway remodeling by stimulating the expression of PDGF via its cellular receptor, PAR-1.