scholarly journals Plasminogen activator inhibitor type I stabilizes vitronectin-dependent adhesions in HT-1080 cells.

1990 ◽  
Vol 111 (5) ◽  
pp. 2183-2195 ◽  
Author(s):  
G J Ciambrone ◽  
P J McKeown-Longo
Keyword(s):  
Binding Site ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Type I ◽  
Adherent Cells ◽  
Cell Rounding ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

Polyclonal antibodies against plasminogen activator inhibitor type-I (PAI-1) caused rapid retraction and rounding of substrate-attached HT-1080 cells. The kinetics and extent of antibody-mediated cell rounding were not dependent on either urokinase or plasmin activity. Cells adherent to vitronectin-coated substrates detached within 2 h of antibody addition. Cells adherent to fibronectin were unaffected by the antibodies. Immunoblotting of substrate-attached material indicated that HT-1080 cells deposited PAI-1 into vitronectin, but not fibronectin, dependent contacts. These data suggest that the antibody-mediated cell rounding resulted from a steric disruption of vitronectin-dependent adhesions, indicating that the binding site on vitronectin for PAI-1 is near, but does not overlap, the binding site for vitronectin receptor. The accumulation of PAI-1 into vitronectin-dependent adhesion sites correlated temporally with the preferential degradation of fibronectin from the substrate. HT-1080 cells adherent to either fibronectin or vitronectin were able to activate exogenous plasminogen to plasmin. Plasmin levels were increased 200% on cells adherent to fibronectin and 100% on cells adherent to vitronectin. In the presence of a neutralizing antibody against PAI-1, vitronectin adherent cells activated plasminogen to the same extent as fibronectin adherent cells. Plasmin levels of 200% above baseline were associated with retraction of cells from the substrate. The ability of vitronectin adherent cells to activate exogenous plasmin was completely blocked in the presence of neutralizing antibodies against urokinase. These data represent the first demonstration that vitronectin-associated PAI-1 regulates urokinase in focal contact areas.

The human plasminogen activator inhibitor type I gene promoter targets to kidney

1998 ◽  
Vol 274 (2) ◽  
pp. F405-F412 ◽  
Author(s):  
Martin P. Emert ◽  
Christine M. Sorenson ◽  
David P. Basile ◽  
Joseph G. Rogers ◽  
Marc R. Hammerman ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Transgene Expression ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Type I ◽  
Plasminogen Activator Inhibitor Type ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

The plasminogen activator inhibitor type 1 (PAI-1) gene encodes the physiological inhibitor of tissue-type and urokinase-type plasminogen activators and is induced by cytokines such as transforming growth factor-β (TGF-β). Studies have identified DNA sequence elements within the first 1.3 kb of the 5′-upstream DNA that mediate cytokine responsiveness in transfected cells in vitro. However, the DNA sequences that mediate PAI-1 expression in vivo have not yet been delineated. To define these regulatory sequences, we generated transgenic mice that expressed a hybrid gene comprising sequences between −1,272 and +75 of the human PAI-1 gene ligated to a LacZ reporter gene. Transgene expression detected in two independent lines was observed only in kidney from embryonic day 13 to adult and was seen primarily in proximal tubule cells of the outer medulla. Transgene expression and activity were unchanged in response to TGF-β and remained restricted to kidney. Thus we have identified a promoter region within the PAI-1 gene that targets transgene expression to kidney but, unlike the native promoter, is unresponsive to TGF-β in the experimental protocol used.

scholarly journals Plasminogen activator inhibitor-type I is a major biosynthetic product of retinal microvascular endothelial cells and pericytes in culture

1989 ◽  
Vol 259 (2) ◽  
pp. 529-535 ◽  
Author(s):  
A E Canfield ◽  
A M Schor ◽  
D J Loskutoff ◽  
S L Schor ◽  
M E Grant
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Type I ◽  
Human Skin Fibroblasts ◽  
Retinal Endothelial Cells ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

Previous studies have shown that a glycoprotein of Mr 47,000 (designated Gp47) is a major biosynthetic product of retinal endothelial cells in vitro (Canfield, Schor, West, Schor & Grant (1987) Biochem. J. 246, 121-129). We now present data indicating that (a) an identical protein is secreted by bovine retinal pericytes, (b) this protein is plasminogen activator inhibitor-type I (PAI-1), as revealed by immunoprecipitation with specific antibodies and reverse fibrin zymography, and (c) retinal endothelial cells and pericytes synthesize different species of matrix macromolecules, that is: type IV collagen is the major collagen secreted by endothelial cells, whereas pericytes produce predominantly type I collagen; fibronectin and thrombospondin are synthesized by both cell types. Our studies also indicate that PAI-1 is produced, albeit at considerably lower levels, by large vessel vascular cells (aortic endothelial and smooth muscle cells) and human skin fibroblasts. PAI-1 produced by human skin fibroblasts appears to be a distinct molecular species compared to its bovine counterpart as assessed by its slower mobility on SDS/polyacrylamide-gel electrophoresis. The potential significance of elevated PAI-1 production by retinal endothelial cells and pericytes, as well as their distinctive patterns of matrix biosynthesis, is discussed in terms of the involvement of these cells in the maintenance and remodelling of microvessel basement membrane.

Lipoprotein (a) up-regulates the expression of the plasminogen activator inhibitor 2 in human blood monocytes

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 981-986 ◽  
Author(s):  
Christa Buechler ◽  
Heidrun Ullrich ◽  
Mirko Ritter ◽  
Mustafa Porsch-Oezcueruemez ◽  
Karl J. Lackner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Blood Monocytes ◽  
Plasminogen Activator Inhibitor Type ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Gender Specific ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Elevated plasma lipoprotein (a) (Lp[a]) and cardiac events show a modest but significant association in various clinical studies. However, the influence of high Lp(a) on the gene expression in blood monocytes as a major cell involved in atherogenesis is poorly described. To identify genes influenced by elevated serum Lp(a), the gene expression was analyzed on a complementary DNA microarray comparing monocytes from a patient with isolated Lp(a) hyperlipidemia and coronary heart disease with monocytes from a healthy blood donor with low Lp(a). By using this approach, numerous genes were found differentially expressed in patient-versus-control monocytes. Verification of these candidates by Northern blot analysis or semiquantitative polymerase chain reaction in monocytes from additional patients with Lp(a) hyperlipidemia and healthy blood donors with elevated Lp(a) confirmed a significant induction of plasminogen activator inhibitor type 2 (PAI-2) messenger RNA (mRNA) in monocytes from male, but not from female, individuals with high Lp(a), indicating that this observation is gender specific. This led also to increased intracellular and secreted PAI-2 protein in monocytes from male probands with Lp(a) hyperlipidemia. Plasminogen activator inhibitor type 1 (PAI-1) mRNA was found suppressed only in the patients′ monocytes and not in healthy probands with high Lp(a) levels. Purified Lp(a) induced PAI-2 mRNA and protein and reduced PAI-1 expression in monocytes isolated from various controls. The finding that PAI-2 is elevated in monocytes from male patients with isolated Lp(a) hyperlipidemia and male healthy probands with high Lp(a) and that purified Lp(a) up-regulates PAI-2 in control monocytes in vitro indicate a direct, but gender-specific, effect of Lp(a) for the induction of PAI-2 expression.

Adiponectin is inversely related to plasminogen activator inhibitor type 1 in patients with stable exertional angina

2004 ◽  
Vol 91 (05) ◽  
pp. 1026-1030 ◽  
Author(s):  
Hidetomo Maruyoshi ◽  
Tohru Funahashi ◽  
Shinzo Miyamoto ◽  
Jun Hokamaki ◽  
Hirofumi Soejima ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Plasma Levels ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor Type ◽  
Exertional Angina ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

SummaryAdipose tissue is a secretory organ producing a variety of bioactive substances, such as adiponectin. Adiponectin has antiatherogenic properties while plasminogen activator inhibitor type 1 (PAI-1) is closely involved in the development of atherosclerosis. The relationship between adiponectin and PAI-1 in patients with coronary artery disease (CAD) has not been clarified. This study examined plasma levels of adiponectin and PAI-1 in 64 patients with stable exertional angina (SEA) and 65 patients with the chest pain syndrome (CPS). Plasma logadiponectin levels were significantly lower in patients with SEA (0.62±0.08 µg/dL) compared to those with CPS (0.86± 0.05 µg/dL) (p<0.0001). The plasma levels of log-PAI-1 were significantly higher in patients with SEA (1.23±0.18 ng/mL) compared to those with CPS (1.15±0.22 ng/mL) (p<0.05). Plasma log-adiponectin levels correlated negatively with diabetes mellitus (DM), body mass index (BMI), log-PAI-1 (r=−0.284, p<0.001), triglyceride (TG), and remnant-like particles cholesterol (RLP-C), and positively with high-density lipoprotein cholesterol (HDL-C) levels. Plasma levels of log-PAI-1 correlated positively with DM, BMI, TG and RLP-C levels, and negatively with HDL-C levels. Multiple logistic regression analysis identified sex, angina pectoris, and PAI-1 as independent determinants of hyperadiponectinemia (p<0.05). Adiponectin is inversely related to PAI-1. DM, BMI, TG, HDL-C, and RLP-C are common mediators between adiponectin and PAI-1, and treatment for common mediators may prevent the development of CAD by reducing PAI-1 and increasing adiponectin levels.

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