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

• DOI: 10.1164/rccm.200206-515oc
• Publication Date: 2003-05-08T17:54:20Z
• Authors: Shino Shimizu; Esteban C. Gabazza; Osamu Taguchi; Hiroki Yasui; Yukiko Taguchi; Tatsuya Hayashi; Masaru Ido; Takeshi Shimizu; Tomohiro Nakagaki; Hiroshi Kobayashi; Kenji Fukudome; Naoko Tsuneyoshi; Corina N. D'Aless...; Masahiko Izumizaki; Michiko Iwase; Ikuo Homma; Yukihiko Adachi; Koji Suzuki
• Keywords: Platelet-Derived Growth Factor; Analysis of Variance; DNA, Complementary; Base Sequence; Pulmonary Fibrosis; Molecular Sequence Data; Epithelial Cells; Mice, Transgenic; Blotting, Northern; Blood Coagulation Factors; Mice, Inbred C57BL; Bleomycin; Disease Models, Animal; Mice; 03 medical and health sciences; 0302 clinical medicine; Gene Expression Regulation; Animals; Female; Lung; Cells, Cultured; Probability

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.