Differential regulation of the plasminogen activator inhibitor-1 (PAI- 1) gene expression by growth factors and progesterone in human endometrial stromal cells

1997 ◽  
Vol 3 (9) ◽  
pp. 781-787 ◽  
Author(s):  
T Sandberg
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Plasminogen Activator ◽  
Stromal Cells ◽  
Plasminogen Activator Inhibitor ◽  
Differential Regulation ◽  
Plasminogen Activator Inhibitor 1 ◽  
Endometrial Stromal Cells ◽  
Activator Inhibitor ◽  
Pai 1

scholarly journals Sex Steroids Regulate the Expression of Plasminogen Activator Inhibitor-1 and its mRNA in Fibroblasts Derived from Uterine Endometrium

1996 ◽  
Vol 33 (6) ◽  
pp. 545-550 ◽  
Author(s):  
Jiro Fujimoto ◽  
Masashi Hori ◽  
Satoshi Ichigo ◽  
Teruhiko Tamaya
Keyword(s):  
Plasminogen Activator ◽  
Stromal Cells ◽  
Sex Steroids ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Endometrial Stromal Cells ◽  
Uterine Endometrium ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor ◽  
Pai 1

In order to clarify a role of stromal cells in sex steroidal neovascularization, plasminogen activator inhibitor (PAI)-1 [an inhibitor of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA)] and its messenger ribonucleic acid (mRNA) were analysed in fibroblasts derived from uterine endometrium as a model for endometrial stromal cells under the influence of sex steroids. The determinations were carried out by an enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction-Southern blotting, respectively. In the fibroblasts, either estradiol or progestogens (progesterone, medroxy progesterone acetate or 17α-hydroxyprogesterone) induced expressions of PAI-1 and its mRNA, and their combination further increased their expression by approximately twofold. PAI-1 from endometrial stromal cells under the influence of sex steroids might contribute to endometrial neovascularization through its effect on endothelial cells in endometrial vessels.

Critical Roles of Rho Kinase and Mek/Erk Pathways for Angiotensin Ii-Induced Plasminogen Activator Inhibitor-1 Gene Expression

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 721-721
Author(s):  
Kotaro Takeda ◽  
Toshihiro Ichiki ◽  
Tomotake Tokunou ◽  
Satoshi Fujii ◽  
Akira Kitabatake ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Plasminogen Activator ◽  
Rho Kinase ◽  
Plasminogen Activator Inhibitor ◽  
Luciferase Assay ◽  
Ang Ii ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

P157 Plasminogen activator inhibitor-1 (PAI-1) plays an integral role not only in the regulation of plasminogen activity and fibrinolytic system but also in the pathogenesis of atherosclerosis and hypertension. Because angiotensin II (Ang II) is also involved in these processes, we investigated its role in the intracellular signaling cascade leading to PAI-1 gene expression in vascular smooth muscle cells (VSMC). Ang II increased the PAI-1 mRNA and protein levels through Ang II type 1 receptor. Although PAI-1 mRNA stability was not increased by Ang II, PAI-1 gene promoter activity, which was measured by luciferase assay, was significantly increased by Ang II. This process did not require de novo protein synthesis. BAPTA-AM, genistein and AG1478 completely inhibited the Ang II-induced PAI-1 mRNA upregulation, suggesting that intracellular calcium, tyrosine kinase and epidermal growth factor (EGF) receptor transactivation were involved in this process. However, inhibition of protein kinase C (PKC) by calphostin C, GF109203, or prolonged exposure to PMA failed to abolish the Ang II-induced PAI-1 upregulation, suggesting PKC pathway was not involved. PD98059 suppressed Ang II-induced PAI-1 upregulation, whereas SB203580 did not, suggesting that MEK/ERK1/2 pathway rather than p38 MAP kinase pathway was crucial in this process. Furthermore, adenovirus-mediated expression of dominant negative form of Rho kinase or Rho kinase inhibitor Y27632 also completely suppressed PAI-1 induction by Ang II without affecting Ang II-induced ERK1/2 activation. These data suggest that activation of both MEK/ERK1/2 and Rho kinase pathways will be necessary for the upregulation of PAI-1 gene expression and these two pathways may act synergically to promote PAI-1 gene transcription at least at the downstream of ERK1/2 in VSMC. These findings are important biological and therapeutical implications for the evolution of arterial wall thrombus and the pathogenesis of atherosclerosis by Ang II.

scholarly journals Glucocorticoid-modulated gene expression of tissue- and urinary-type plasminogen activator and plasminogen activator inhibitor 1 and 2.

1988 ◽  
Vol 106 (3) ◽  
pp. 971-978 ◽  
Author(s):  
R L Medcalf ◽  
E Van den Berg ◽  
W D Schleuning
Keyword(s):  
Gene Expression ◽  
Plasminogen Activator ◽  
Protein Biosynthesis ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Northern Blot Hybridization ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor ◽  
Pai 1

Constitutive gene expression of four components of plasminogen activating enzyme system, urinary and tissue-type plasminogen activator (u-PA and t-PA), plasminogen activator inhibitor 1 (PAI-1) and PAI-2 in HT-1080 human fibrosarcoma cells, was modulated by the synthetic glucocorticoid dexamethasone (Dex, 10(-7) M). More than 90% of u-PA, t-PA and PAI-1 antigen was found in conditioned medium, whereas PAI-2 was mainly cell associated. In 48-h culture supernatants (expressed per 10(6) cells) PAI-1 antigen increased from 350 to 3,300 ng and t-PA from 19 to 38 ng. u-PA and PAI-2 in the same samples decreased from 380 to 46 ng and from 3.5 to 1.8 ng, respectively. Northern blot hybridization and nuclear "Run-on" transcription assays demonstrated that the increase of t-PA and PAI-1 and the decrease of u-PA were associated with equivalent changes of gene template activity. Modulation of u-PA, t-PA and PAI-1 gene expression by Dex was completely blocked by the glucocorticoid antagonist RU 38486, suggesting that all effects were mediated through the glucocorticoid receptor. Cycloheximide, an inhibitor of protein biosynthesis induced a rapid transient increase of t-PA, u-PA and PAI-1 mRNA and a sustained increase of PAI-2 mRNA, but blocked the more long term effects of Dex, suggesting that both constitutive and hormonally regulated maintenance of mRNA steady state levels required protein biosynthesis.

scholarly journals Endogenous Aldosterone Contributes to Acute Angiotensin II-Stimulated Plasminogen Activator Inhibitor-1 and Preproendothelin-1 Expression in Heart But Not Aorta

Endocrinology ◽  
2008 ◽  
Vol 150 (5) ◽  
pp. 2229-2236 ◽  
Author(s):  
James M. Luther ◽  
Zuofei Wang ◽  
Ji Ma ◽  
Natalia Makhanova ◽  
Hyung-Suk Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Plasminogen Activator ◽  
Plasma Renin ◽  
Plasminogen Activator Inhibitor ◽  
Renin Activity ◽  
Ang Ii ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

To test the hypothesis that angiotensin (Ang) II induces profibrotic gene expression through endogenous aldosterone, we measured the effect of 4 h infusion (600 ng/kg · min) of Ang II on tissue mRNA expression of plasminogen activator inhibitor 1 (PAI-1), preproendothelin-1 (ppET-1), TGF-β, and osteopontin in wild-type (WT), aldosterone synthase-deficient (AS−/−), and AS−/− mice treated with aldosterone (either 500 ng/d for 7 d or 250 ng as a concurrent 4 h infusion). Ang II increased aldosterone in WT (P < 0.001) but not in AS−/− mice. Aldosterone (7 d) normalized basal aldosterone concentrations in AS−/− mice; however, there was no further effect of Ang II on aldosterone (P = NS). Basal cardiac and aortic PAI-1 and ppET-1 expression were similar in WT and AS−/− mice. Ang II-stimulated PAI-1 (P < 0.001) and ppET-1 expression (P = 0.01) was diminished in the heart of AS−/− mice; treatment with aldosterone for 4 h or 7 d restored PAI-1 and ppET-1 mRNA responsiveness to Ang II in the heart. Ang II increased PAI-1 (P = 0.01) expression in the aorta of AS−/− as well as WT mice. In the kidney, basal PAI-1, ppET-1, and TGF-β mRNA expression was increased in AS−/− compared with WT mice and correlated with plasma renin activity. Ang II did not stimulate osteopontin or TGF-β expression in the heart or kidney. Endogenous aldosterone contributes to the acute stimulatory effect of Ang II on PAI-1 and ppET-1 mRNA expression in the heart; renin activity correlates with basal profibrotic gene expression in the kidney.

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