Mitogen-activated protein kinases pathway is involved in physiological testosterone-induced tissue factor pathway inhibitor expression in endothelial cells.
The mechanism of testosterone inducing the tissue factor pathway inhibitor (TFPI) in protecting against thrombosis is unknown. We aimed to elucidate the mechanisms involved in the induction by observing, in human umbilical vein endothelial cells (HUVECs), the phosphorylation of mitogen-activated protein kinases (MAPKs), a major cell signaling system. The level of testosterone regulating several signaling pathways, including extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun-N-terminal kinase (JNK), and p38 MAPK, was measured by western blot in HUVECs. ELISA and quantitative real-time reverse transcriptase-PCR were used to analyze TFPI expression after blocking ERK1/2 (with PD98059) or JNK (with SP600125) pathway in HUVECs. Testosterone-induced a rapid phosphorylation of ERK1/2, JNK and p38 MAPK in HUVECs, which could not be inhibited by androgen receptor antagonist flutamide. Blocking ERK1/2 or JNK pathway could significantly impair testosterone-induced TFPI at both translational and transcriptional levels in HUVECs. Testosterone at a physiological concentration may help to prevent thrombosis development by stimulating TFPI expression in HUVECs, partly through the ERK1/2 and JNK MAPK pathway.
Jin
Hong
H
The First Affiliated Hospital of Shantou University Medical College, China.
Wang
Da-yu
DY
Mei
Yi-fang
YF
Qiu
Wen-bing
WB
Zhou
Yi
Y
Wang
Dong-ming
DM
Tan
Xue-rui
XR
Li
Yu-guang
YG
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology*; D013927:Thrombosis / Q000517:prevention & control
D008074:Lipoproteins; D012333:RNA, Messenger; C051928:lipoprotein-associated coagulation inhibitor; D013739:Testosterone; D020928:Mitogen-Activated Protein Kinases