The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

SERPINE1  -  serpin peptidase inhibitor, clade E (nexin...

Bos taurus

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of SERPINE1

  • Hyperglycemia increased expression from an 85-bp truncated plasminogen activator inhibitor-1 (PAI-1) promoter luciferase reporter containing two Sp1 sites in a similar fashion (3.8-fold) [1].
  • Furthermore, the effect of short-term anoxia on PA and PAI could not be reversed by reoxygenation for 24 hours [2].
  • Local accumulation of plasminogen activator inhibitor-1 (PAI-1) in response to thrombosis has been implicated not only in inhibition of fibrinolysis but also in the pathogenesis of vascular disease [3].
  • Glucocorticoids decrease plasminogen activator (PA) activity in HTC rat hepatoma cells by inducing a specific inhibitor of PA activity (PAI) [4].
  • Circadian variation in plasminogen activator inhibitor-1 (PAI-1) production likely contributes to increased risk of myocardial infarction and decreased efficacy of thrombolytic therapy during the morning [5].

High impact information on SERPINE1

  • Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV [6].
  • These results indicate that the hexapeptide Ang IV is the form of angiotensin that stimulates endothelial expression of PAI-1 [6].
  • Although larger forms of angiotensin (i.e., Ang I, Ang II, and Ang III) are capable of inducing PAI-1 expression, this property is lost in the presence of converting enzyme or aminopeptidase inhibitors [6].
  • Furthermore, both TGase inhibitors and a neutralizing antibody to TGase potentiated the effect of retinol in enhancing plasminogen activator (PA) levels in cultures of BAECs by suppressing the TGF-beta-mediated enhancement of PA inhibitor-1 (PAI-1) expression [7].
  • However, the kinetics and amplitude of PAI-1 and u-PA mRNA induction by these agents are strikingly different [8].

Biological context of SERPINE1

  • Preincubation of thrombin with hirudin, a specific inhibitor of thrombin, or with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, an inhibitor of the active site of thrombin, prevented the induction of PAI-1 synthesis [3].
  • This effect was attributed to a moderate upregulation of urokinase-type PA expression as well as to a significant down-regulation of PA inhibitor-1 (PAI-1) expression [9].
  • IL-1 induced increases in PAI-1 production in EC transfected with reporter genes alone [10].
  • The resultant TGF-beta suppresses the excessive fibrinolytic activity by decreasing PA expression and stimulating expression of the PA inhibitor, PA inhibitor-1 (PAI-1), and inhibits cell proliferation [11].
  • Both CLOCK:BMAL1 and CLOCK:BMAL2 heterodimers activate the PAI-1 promoter through requisite proximal (-565 to -560 bp) and distal (-680 to -675 bp) E-box enhancers [5].

Anatomical context of SERPINE1


Associations of SERPINE1 with chemical compounds

  • Recent studies from this laboratory have demonstrated that angiotensin II (Ang II) stimulates the expression of plasminogen activator inhibitor 1 (PAI-1) in cultured endothelial cells [6].
  • The PAI-1 could not be removed by incubating ECM in high salt (2 mol/L NaCl), sugars (1 mol/L galactose, 1 mol/L mannose), glycosaminoglycans (10 mmol/L heparin, 10 mmol/L dermatan sulfate), or epsilon-aminocaproic acid (0.1 mol/L) [12].
  • (1) Infusion of thrombin in rabbits made deficient in vitamin K-dependent plasma proteins by warfarin treatment did not result in modification of PAI activity [14].
  • However, PAI-1 could be extracted from ECM by treatment with either arginine (0.5 mol/L) or potassium thiocyanate (2 mol/L), or by incubation under acidic conditions (pH 2.5) [12].
  • For example, less than 0.01 units/microliter of PAI activity was detected in untreated conditioned medium, but medium treated with sodium dodecyl sulfate (1.7 mM), guanidine HCl (4 M), urea (12 M) or KSCN (6 M) contained 0.9, 1.9, 0.8, and 0.5 units/microliter, respectively [15].

Physical interactions of SERPINE1

  • Alanine substitutions at the distal P4' (Glu-350) and P5' (Glu-351) residues of PAI-1 reduced the rates of Michaelis complex formation (k(a)) and overall inhibition (k(app)) with tPA by 13.4- and 4.7-fold, respectively, whereas the rate of loop insertion or final acyl-enzyme formation (k(lim)) increased by 3.3-fold [16].

Regulatory relationships of SERPINE1

  • The inclusion of neutralizing antibodies to TGF-beta in the co-culture medium blocked the observed increase in PAI-1 levels [17].
  • SPARC stimulated the secretion of PAI-1 protein into the medium of subconfluent BAE cells, but not confluent BAE cells, in a dose- and time-dependent manner [18].
  • Treating chondrocytes with IL-1 induced the expression of MMPs and downregulated TIMP-1 but stimulated both the expression of PAs and PAI-1 [19].

Other interactions of SERPINE1

  • Since the induction of PAI-1 mRNA by SPARC was not blocked by cycloheximide, de novo protein synthesis was apparently not required for this stimulation [18].
  • Both drugs inhibited the IL-1-induced mRNA expression of tPA, whereas expression of uPA was only mildly reduced by PSGAG, which also induced PAI-1 above IL-1 stimulated levels [19].
  • OBJECTIVE: To determine the in vitro effects of several nonsteroidal antiinflammatory drugs on the IL-1 altered expression and activity of tPA, uPA and PAI-1 by articular chondrocytes [20].
  • Kinetic analyses showed that anhydrotrypsin had little or no ability to compete with trypsin for binding to alpha 1-proteinase inhibitor (alpha 1PI), plasminogen activator inhibitor 1 (PAI-1), antithrombin (AT), or AT-heparin complex when present at up to a 100-fold molar excess over trypsin [21].
  • The endotoxin-induced PAI from both cell types was not immunoprecipitated by incubation with IgG directed against the endothelial-type inhibitor, PAI-1, or antiserum directed against the placental-type inhibitor, PAI-2 [22].

Analytical, diagnostic and therapeutic context of SERPINE1

  • The level of plasminogen activator inhibitor 1 (PAI-1) was also evaluated by Northern blotting and protein radiolabeling [13].
  • This protein was identified as type 1 plasminogen activator inhibitor (PAI-1) on Western blots with anti-PAI-1 antiserum [18].
  • Both control and treated cells produced multiple forms of PA, as evaluated by SDS-PAGE zymography, and a single form of PAI, as evidenced by reverse fibrin autography [23].
  • By in situ hybridization, we demonstrate that the increase in PAI-1 mRNA is localized to cells at the edge of a wounded BME or BAE cell monolayer [24].
  • PGD2 and PAI-1 levels were determined by radio- and enzyme-immunoassay, respectively [10].


  1. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Du, X.L., Edelstein, D., Rossetti, L., Fantus, I.G., Goldberg, H., Ziyadeh, F., Wu, J., Brownlee, M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Reduction in pO2 decreases the fibrinolytic potential of cultured bovine endothelial cells derived from pulmonary arteries and lung microvasculature. Wojta, J., Jones, R.L., Binder, B.R., Hoover, R.L. Blood (1988) [Pubmed]
  3. Induction of vascular smooth muscle cell expression of plasminogen activator inhibitor-1 by thrombin. Noda-Heiny, H., Fujii, S., Sobel, B.E. Circ. Res. (1993) [Pubmed]
  4. The dexamethasone-induced inhibitor of plasminogen activator in hepatoma cells is antigenically-related to an inhibitor produced by bovine aortic endothelial cells. Loskutoff, D.J., Roegner, K., Erickson, L.A., Schleef, R.R., Huttenlocher, A., Coleman, P.L., Gelehrter, T.D. Thromb. Haemost. (1986) [Pubmed]
  5. Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. Schoenhard, J.A., Smith, L.H., Painter, C.A., Eren, M., Johnson, C.H., Vaughan, D.E. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  6. Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV. Kerins, D.M., Hao, Q., Vaughan, D.E. J. Clin. Invest. (1995) [Pubmed]
  7. Requirement for transglutaminase in the activation of latent transforming growth factor-beta in bovine endothelial cells. Kojima, S., Nara, K., Rifkin, D.B. J. Cell Biol. (1993) [Pubmed]
  8. Transforming growth factor-beta 1 modulates basic fibroblast growth factor-induced proteolytic and angiogenic properties of endothelial cells in vitro. Pepper, M.S., Belin, D., Montesano, R., Orci, L., Vassalli, J.D. J. Cell Biol. (1990) [Pubmed]
  9. Midkine enhances fibrinolytic activity of bovine endothelial cells. Kojima, S., Muramatsu, H., Amanuma, H., Muramatsu, T. J. Biol. Chem. (1995) [Pubmed]
  10. Endogenous prostaglandin D2 synthesis reduces an increase in plasminogen activator inhibitor-1 following interleukin stimulation in bovine endothelial cells. Negoro, H., Soo Shin, W., Hakamada-Taguchi, R., Eguchi, N., Urade, Y., Goto, A., Toyo-Oka, T., Fujita, T., Omata, M., Uehara, Y. J. Hypertens. (2002) [Pubmed]
  11. Retinoids potentiate transforming growth factor-beta activity in bovine endothelial cells through up-regulating the expression of transforming growth factor-beta receptors. Yoshizawa, M., Miyazaki, H., Kojima, S. J. Cell. Physiol. (1998) [Pubmed]
  12. Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor. Mimuro, J., Schleef, R.R., Loskutoff, D.J. Blood (1987) [Pubmed]
  13. Avocado/soya unsaponifiables enhance the expression of transforming growth factor beta1 and beta2 in cultured articular chondrocytes. Boumediene, K., Felisaz, N., Bogdanowicz, P., Galera, P., Guillou, G.B., Pujol, J.P. Arthritis Rheum. (1999) [Pubmed]
  14. Thrombin infusion in endotoxin-treated rabbits reduces the plasma levels of plasminogen activator inhibitor: evidence for a protein-C-mediated mechanism. Colucci, M., Triggiani, R., Cavallo, L.G., Semeraro, N. Blood (1989) [Pubmed]
  15. Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. Hekman, C.M., Loskutoff, D.J. J. Biol. Chem. (1985) [Pubmed]
  16. The contribution of the exosite residues of plasminogen activator inhibitor-1 to proteinase inhibition. Ibarra, C.A., Blouse, G.E., Christian, T.D., Shore, J.D. J. Biol. Chem. (2004) [Pubmed]
  17. Characterization of the activation of latent TGF-beta by co-cultures of endothelial cells and pericytes or smooth muscle cells: a self-regulating system. Sato, Y., Tsuboi, R., Lyons, R., Moses, H., Rifkin, D.B. J. Cell Biol. (1990) [Pubmed]
  18. SPARC induces the expression of type 1 plasminogen activator inhibitor in cultured bovine aortic endothelial cells. Hasselaar, P., Loskutoff, D.J., Sawdey, M., Sage, E.H. J. Biol. Chem. (1991) [Pubmed]
  19. Effects of polysulfated glycosaminoglycan and triamcinolone acetonid on the production of proteinases and their inhibitors by IL-1alpha treated articular chondrocytes. Sadowski, T., Steinmeyer, J. Biochem. Pharmacol. (2002) [Pubmed]
  20. Differential effects of nonsteroidal antiinflammatory drugs on the IL-1 altered expression of plasminogen activators and plasminogen activator inhibitor-1 by articular chondrocytes. Sadowski, T., Steinmeyer, J. Inflamm. Res. (2002) [Pubmed]
  21. Role of the catalytic serine in the interactions of serine proteinases with protein inhibitors of the serpin family. Contribution of a covalent interaction to the binding energy of serpin-proteinase complexes. Olson, S.T., Bock, P.E., Kvassman, J., Shore, J.D., Lawrence, D.A., Ginsburg, D., Björk, I. J. Biol. Chem. (1995) [Pubmed]
  22. Endotoxin-induced secretion of an active plasminogen activator inhibitor from bovine pulmonary arterial and aortic endothelial cells. Crutchley, D.J., Conanan, L.B., Ryan, U.S. Biochem. Biophys. Res. Commun. (1987) [Pubmed]
  23. Influence of nicotine and cotinine on the expression of plasminogen activator activity in bovine aortic endothelial cells. Kuo, B.S., Dryjski, M., Bjornsson, T.D. Thromb. Haemost. (1989) [Pubmed]
  24. Plasminogen activator inhibitor-1 is induced in migrating endothelial cells. Pepper, M.S., Sappino, A.P., Montesano, R., Orci, L., Vassalli, J.D. J. Cell. Physiol. (1992) [Pubmed]
WikiGenes - Universities