These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.
Pubmed for Handhelds
PUBMED FOR HANDHELDS
Search MEDLINE/PubMed
Title: Differential mechanisms of plasminogen activator inhibitor-1 gene activation by transforming growth factor-beta and tumor necrosis factor-alpha in endothelial cells. Author: Chen YQ, Sloan-Lancaster J, Berg DT, Richardson MA, Grinnell B, Tseng-Crank J. Journal: Thromb Haemost; 2001 Dec; 86(6):1563-72. PubMed ID: 11776328. Abstract: Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (SERPIN) specific for tissue-type and urokinase-like plasminogen activators. High plasma PAI-1 activity is a risk factor for thrombotic diseases. Due to the short half-life of PAI-1, regulation of PAI-1 gene expression and secretion of active PAI-1 into the blood stream is important for hemostatic balance. We have investigated transcriptional control of PAI-1 gene expression in bovine aortic endothelial cells (BAECs) and human cell lines using PAI-1 5' promoter-luciferase reporter assays. Contrary to the cytokine-induced up-regulation of PAI-1 mRNA and protein levels, we found that only transforming growth factor-beta (TGF-beta) was efficient in inducing PAI-1 promoter activation. Tissue necrosis factor-alpha (TNF-alpha) induced a small luciferase activity with the 2.5 kb PAI-1 promoter, but not with the PAI-800/4G/5G and p3TP-lux promoters. Next we investigated whether a lack of response to TNF-alpha was due to deficient signaling pathways. BAECs responded to TNF-alpha with robust NFkappaB promoter activation. TGF-beta activated the p38 MAP kinase, while TNF-alpha activated both the SAPK/JNK and p38 MAP kinases. The ERK1/2 MAP kinases were constitutively activated in BAECs. BAEC therefore responded to TNF-alpha stimulation with activation of the MAP kinases and the NFkappaB transcriptional factors. We further measured the messenger RNA stability under the influence by TGF-beta and TNF-alpha and found no difference. PAI-1 gene activation by TNF-alpha apparently is yet to be defined for the location of the response element and/or the signaling pathway, while TGF-beta is the most important cytokine for PAI-1 transcriptional activation through its 5' proximal promoter.[Abstract] [Full Text] [Related] [New Search]