Transforming growth factor-beta1 enhances the antifibrinolytic and prothrombotic state of growing endothelial cells in a cell cycle-specific manner.
Cell cycle-dependent modulation of protein expression may influence the balance of antithrombotic and prothrombotic properties of endothelial cells. In the present study, we examined the regulation of prothrombotic and antithrombotic molecules by transforming growth factor-beta1 (TGF-beta1) during distinct phases of the cell cycle in human umbilical vein endothelial cells. In the absence of TGF-beta1, the expression of thrombomodulin, the plasminogen activators u-PA and t-PA, and their inhibitor PAI-1 was significantly increased in the S/G2 compared to the G1 phase. Treatment of endothelial cells with TGF-beta1, however, resulted in elevated expression of PAI-1 specifically in the S/G2 phase, while t-PA and u-PA increased to the same extent in both the G1 and S/G2 phase. These findings demonstrate that the expression of a subset of hemostatically relevant proteins is regulated during endothelial cell cycle and that TGF-beta1 can differentially modulate cell cycle-controlled protein expression.
Stoldt
Volker R
VR
Department of Hemostasis and Transfusion Medicine, Laboratory of Vascular Biology, Heinrich Heine University Medical Center, Bldg. 12.49.00, Rm. 9, Moorenstr. 5, D-40225 Dusseldorf, Germany. stoldt@uni-duesseldorf.de
Schnorr
Oliver
O
Schulze-Osthoff
Klaus
K
Scharf
Rudiger E
RE
D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D018180:Thrombomodulin / Q000235:genetics / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; C508960:TGFB1 protein, human; D018180:Thrombomodulin; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator