Pro-urokinase up-regulates the expression of urokinase-type plasminogen activator (u-PA) in human pulmonary arterial endothelial cells.
The fibrinolytic function of endothelial cells plays an important role in the pathophysiology of pulmonary vascular diseases. In this study, the effects of pro-urokinase, a new thrombolytic drug that is currently being tested for the treatment of pulmonary embolism, on the expression of urokinase-type plasminogen activator (u-PA) and u-PA receptor (u-PAR) were assessed. The role of u-PAR was also investigated. Immunocytofluorescence and RT-PCR techniques were employed. In normal human pulmonary arterial endothelial cells (HPAECs), the expression levels of u-PA and u-PAR were very low. Incubation with pro-urokinase up-regulated u-PA expression at both the mRNA level and the protein level; however, the expression of u-PAR was not affected. The effect of pro-urokinase induction was totally inhibited by the release of u-PAR from the HPAECs' surface with PLC. This result suggests that the combination of u-PA with u-PAR may be a critical pathway for the induction of u-PA expression.
Liu
Yi
Y
Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Department of Physiology, Capital Medical University, Beijing, 100069, PR China.
Wang
Chen
C
Yang
Yuanhua
Y
Hou
Xiaoli
X
Wang
Jun
J
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D011651:Pulmonary Artery / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000494:pharmacology
D012333:RNA, Messenger; D011994:Recombinant Proteins; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase