Activated protein C inhibits the expression of platelet-derived growth factor in the lung.
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.
Shimizu
Shino
S
Department of Molecular Pathobiology, Mie University School of Medicine, Tsu City, Japan.
Gabazza
Esteban C
EC
Taguchi
Osamu
O
Yasui
Hiroki
H
Taguchi
Yukiko
Y
Hayashi
Tatsuya
T
Ido
Masaru
M
Shimizu
Takeshi
T
Nakagaki
Tomohiro
T
Kobayashi
Hiroshi
H
Fukudome
Kenji
K
Tsuneyoshi
Naoko
N
D'Alessandro-Gabazza
Corina N
CN
Izumizaki
Masahiko
M
Iwase
Michiko
M
Homma
Ikuo
I
Adachi
Yukihiko
Y
Suzuki
Koji
K
D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001761:Bleomycin; D001779:Blood Coagulation Factors / Q000235:genetics / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000473:pathology*; D011897:Random Allocation; D011956:Receptors, Cell Surface / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D001779:Blood Coagulation Factors; D018076:DNA, Complementary; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; C091963:activated protein C receptor; D001761:Bleomycin