Activated Protein C Inhibits the Expression of Platelet-derived Growth Factor in the Lung

• Published in: American journal of respiratory and critical care medicine Vol. 167; no. 10; pp. 1416 - 1426
• Main Authors: Shimizu, Shino, Gabazza, Esteban C, Taguchi, Osamu, Yasui, Hiroki, Taguchi, Yukiko, Hayashi, Tatsuya, Ido, Masaru, Shimizu, Takeshi, Nakagaki, Tomohiro, Kobayashi, Hiroshi, Fukudome, Kenji, Tsuneyoshi, Naoko, D'Alessandro-Gabazza, Corina N, Izumizaki, Masahiko, Iwase, Michiko, Homma, Ikuo, Adachi, Yukihiko, Suzuki, Koji
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.05.2003; American Lung Association; American Thoracic Society
• Subjects: Analysis of Variance; Animals; Base Sequence; Biological and medical sciences; Bleomycin; Blood Coagulation Factors - genetics; Blood Coagulation Factors - pharmacology; Blotting, Northern; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; Disease Models, Animal; DNA, Complementary - analysis; Epithelial Cells - drug effects; Epithelial Cells - physiology; Female; Gene Expression Regulation; Lung - drug effects; Lung - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Platelet-Derived Growth Factor - drug effects; Platelet-Derived Growth Factor - physiology; Pneumology; Probability; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - pathology; Random Allocation; Receptors, Cell Surface - genetics; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Lung disease; Respiratory disease; Lung; Cytokine; Rodentia; Exploration; Protein C; Receiver; epithelial cells; Histology; coagulation; lung fibrosis; Pathology; Vertebrata; Mammalia; Treatment; Mouse; activated protein C receptor; Animal; Fibrosis; Interstitial pneumonitis; Platelet derived growth factor; Growth factor
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200206-515OC

The natural anticoagulant-activated protein C may inhibit inflammation and fibrosis in the lung. Platelet-derived growth factor is involved in the pathogenesis of lung fibrosis. This study assessed the effect of activated protein C on platelet-derived growth factor expression in human cell lines and in an in vivo model of lung fibrosis. Activated protein C significantly inhibited the secretion and expression of platelet-derived growth factor in human lung cell lines, primary bronchial epithelial cells, and macrophages. In vitro studies also showed that the endothelial activated protein C receptor is expressed by lung epithelial cells and macrophages, and that this receptor and the proteolytic activity of activated protein are implicated in the inhibition of platelet-derived growth factor expression. In the in vivo model of lung fibrosis, intratracheal administration of activated protein C decreased the expression of platelet-derived growth factor and suppressed the development of lung fibrosis. Concomitant intratracheal administration of activated protein C and anti-endothelial activated protein C receptor or anti-platelet-derived growth factor suppressed the inhibitory activity of activated protein C in vivo. In brief, this study describes a novel biological function of activated protein C that may further explain its inhibitory activity on lung inflammation and fibrosis.