title: t-PA stimulates VEGF expression in endothelial cells via ERK2/p38 signaling pathways.
abstract: Vascular endothelial growth factor (VEGF) plays an essential role in the initiation and regulation of angiogenesis, which is a crucial component of wound healing and vessel growth. Tissue-type plasminogen activator (t-PA) could stimulate angiogenesis but the precise mechanisms of their proangiogenic actions remain unclear. We investigated whether t-PA can induce VEGF expression in ECV304 and further explored the underlying signaling pathway(s) involved. Through adenovirus mediated overexpression of t-PA in ECV304 cells, we demonstrated that t-PA significantly increased both VEGF mRNA and protein expression. A further mechanistic study showed that both ERK and p38 MAPK activation were involved in this process. Incubation of RVEC with PD 98059 (MEK kinase inhibitor) significantly reduced t-PA-induced ERK2 activity, VEGF mRNA and protein expression. Furthermore, PD 98059 treatment almost completely abolished p38 activation. Our data suggest that t-PA-stimulates VEGF expression in RVEC via transactivation of p38 by ERK. One potential implication of this finding is that increased t-PA levels in thomb could facilitate vessel growth by stimulating VEGF synthesis and angiogenesis.
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Duan
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Caifang
authors.initials: C
authors.lastname: Ni
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007202:Indicators and Reagents; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D010959:Tissue Plasminogen Activator