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DOI: 10.1160/TH08-07-0490
Metabolic, hormonal and environmental regulation of plasminogen activator inhibitor-1 (PAI-1) expression: Lessons from the liver
Publikationsverlauf
Received:
30. Juli 2008
Accepted after major revision:
12. September 2008
Publikationsdatum:
23. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200806/lookinside/thumbnails/10-1160-th08-07-0490-1.jpg)
Summary
Plasminogen activator inhibitor-1 (PAI-1) controls the regulation of the fibrinolytic system in blood by inhibiting both urokinase-type and tissue-type plasminogen activators. Enhanced levels of PAI-1 are found in PAI-1 patients with type 2 diabetes mellitus which is associated with a dysbalance in glucose and lipid homeostasis. Especially a defective insulin response in the liver contributes to the development of hyperglycemia, dyslipidemia and peripheral insulin resistance and may contribute to hepatic overexpression of PAI-1 in diabetes type 2. Furthermore,a substantial upregulation of PAI-1 expression has also been shown in a variety of liver injury models.Thus, the liver appears to be not only a major site of PAI-1 synthesis in response to hormonal changes, but also in response to a variety of other pathological events. PAI-1 expression in liver largely depends on activation of signalling pathways and transcriptional regulators which may be the basis fora new level of cross-talk between different signalling pathways and thus may represent attractive therapeutic candidates.This article will primarily focus on the regulation of PAI-1 expression in liver cells and discuss potential cross-talks between metabolic, hormonal and environmental signals.
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References
- 1 Loskutoff DJ, Quigley JP. PAI-1, fibrosis, and the elusive provisional fibrin matrix. J Clin Invest 2000; 106: 1441-1443.
- 2 Mars WM, Zarnegar R, Michalopoulos GK. Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA. Am J Pathol 1993; 143: 949-958.
- 3 Wigler M, Ford JP, Weinstein IB. Glucocorticoid inhibition of the fibrinolytic activity of tumor cells. Proteases and biological control. New York: Cold Spring Harbor; 1975: 849-856.
- 4 Seifert SC, Gelehrter TD. Mechanism of dexamethasone inhibition of plasminogen activator in rat hepatoma cells. Proc Natl Acad Sci USA 1978; 75: 6130-6133.
- 5 Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost 2005; 93: 631-640.
- 6 Andreasen PA, Riccio A, Welinder KG. et al. Plasminogen activator inhibitor type-1: reactive center and amino-terminal heterogeneity determined by protein and cDNA sequencing. FEBS Lett 1986; 209: 213-218.
- 7 Ginsburg D, Zeheb R, Yang AY. et al. cDNA cloning of human plasminogen activator-inhibitor from endothelial cells. J Clin Invest 1986; 78: 1673-1680.
- 8 Ny T, Sawdey M, Lawrence D. et al. Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor. Proc Natl Acad Sci USA 1986; 83: 6776-6780.
- 9 Pannekoek H, Veerman H, Lambers H. et al. Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family. EMBO J 1986; 05: 2539-2544.
- 10 Wun TC, Kretzmer KK. cDNA cloning and expression in E coli ofa plasminogen activator inhibitor (PAI) related to a PAI produced by Hep G2 hepatoma cell. FEBS Lett 1987; 210: 11-16.
- 11 Philips M, Juul AG, Thorsen S. et al. Immunological relationship between the fast-acting plasminogen activator inhibitors from plasma, blood platelets and endothelial cells demonstrated with a monoclonal antibody against an inhibitor from placenta. Thromb Haemost 1986; 55: 213-217.
- 12 Collen D. Report of the Meeting of the Subcommittee on Fibrinolysis, Jerusalem, Israel, June 8. Thromb Haemost 1986; 56: 415-416.
- 13 Erickson LA, Schleef RR, Ny T. et al. The fibrinolytic system of the vascular wall. Clin Haematol 1985; 14: 513-530.
- 14 Reilly CF, McFall RC. Platelet-derived growth factor and transforming growth factor-beta regulate plasminogen activator inhibitor-1 synthesis in vascular smooth muscle cells. J Biol Chem 1991; 266: 9419-9427.
- 15 Sawdey MS, Loskutoff DJ. Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. J Clin Invest 1991; 88: 1346-1353.
- 16 Busso N, Nicodeme E, Chesne C. et al. Urokinase and type I plasminogen activator inhibitor production by normal human hepatocytes: modulation by inflammatory agents. Hepatology 1994; 20: 186-190.
- 17 Alessi MC, Peiretti F, Morange P. et al. Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes 1997; 46: 860-867.
- 18 Seiffert D, Smith JW. The cell adhesion domain in plasma vitronectin is cryptic. J Biol Chem 1997; 272: 13705-13710.
- 19 Mimuro J, Loskutoff DJ. Purification of a protein from bovine plasma that binds to type 1 plasminogen activator inhibitor and prevents its interaction with extracellular matrix. Evidence that the protein is vitronectin.J Biol Chem 1989; 264: 936-939.
- 20 Cubellis MV, Andreasen P, Ragno P. et al. Accessibility of receptor-bound urokinase to type-1 plasminogen activator inhibitor. Proc Natl Acad Sci USA 1989; 86: 4828-4832.
- 21 Degryse B, Sier CF, Resnati M. et al. PAI-1 inhibits urokinase-induced chemotaxis by internalizing the urokinase receptor. FEBS Lett 2001; 505: 249-254.
- 22 Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost 2005; 93: 631-640.
- 23 Juhan VI, Roul C, Alessi MC. et al. Increased plasminogen activator inhibitor activity in non insulin dependent diabetic patients--relationship with plasma insulin. Thromb Haemost 1989; 61: 370-373.
- 24 Schneider DJ, Nordt TK, Sobel BE. Attenuated fibrinolysis and accelerated atherogenesis in type II diabetic patients. Diabetes 1993; 42: 1-7.
- 25 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-820.
- 26 Kim JK, Gavrilova O, Chen Y. et al. Mechanism of insulin resistance in A-ZIP/F-1 fatless mice. J Biol Chem 2000; 275: 8456-8460.
- 27 Spiegelman BM, Flier JS. Adipogenesis and obesity: rounding out the big picture. Cell 1996; 87: 377-389.
- 28 Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B. et al. Life without white fat: a transgenic mouse. Genes Dev 1998; 12: 3168-3181.
- 29 Eddy AA. Plasminogen activator inhibitor-1 and the kidney. Am J Physiol Renal Physiol 2002; 283: F209-F220.
- 30 Lagoa CE, Vodovotz Y, Stolz DB. et al. The role of hepatic type 1 plasminogen activator inhibitor (PAI-1) during murine hemorrhagic shock. Hepatology 2005; 42: 390-399.
- 31 Wang H, Vohra BP, Zhang Y. et al. Transcriptional profiling after bile duct ligation identifies PAI-1 as a contributor to cholestatic injury in mice. Hepatology 2005; 42: 1099-1108.
- 32 Bergheim I, Guo L, Davis MA. et al. Critical role of plasminogen activator inhibitor-1 in cholestatic liver injury and fibrosis. J Pharmacol Exp Ther 2006; 316: 592-600.
- 33 Reilly TP, Bourdi M, Brady JN. et al. Expression profiling of acetaminophen liver toxicity in mice using microarray technology. Biochem Biophys Res Commun 2001; 282: 321-328.
- 34 Ganey PE, Luyendyk JP, Newport SW. et al. Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice. Hepatology 2007; 46: 1177-1186.
- 35 Bergheim I, Guo L, Davis MA. et al. Metformin prevents alcohol-induced liver injury in the mouse: Critical role of plasminogen activator inhibitor-1. Gastroenterology 2006; 130: 2099-2112.
- 36 Moller DE. New drug targets for type 2 diabetes and the metabolic syndrome. Nature 2001; 414: 821-827.
- 37 Jungermann K, Kietzmann T. Zonation of parenchymal and nonparenchymal metabolism in liver. Annu Rev Nutr 1996; 16: 179-203.
- 38 Jungermann K, Kietzmann T. Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology 2000; 31: 255-260.
- 39 Kietzmann T. Oxygen-dependent regulation of hepatic glucose metabolism. Methods Enzymol 2004; 381: 357-376.
- 40 Kuster J, Beuers U, Jungermann K. Modulation of the sympathetic nerve action on carbohydrate and ketone body metabolism by fatty acids, glucagon und insulin in perfused rat liver. Biol Chem Hoppe Seyler 1989; 370: 1035-1044.
- 41 Jungermann K. Role of intralobular compartmentation in hepatic metabolism. Diabete Metab 1992; 18: 81-86.
- 42 Jelinek LJ, Lok S, Rosenberg GB. et al. Expression cloning and signaling properties of the rat glucagon receptor. Science 1993; 259: 1614-1616.
- 43 Mayo KE, Miller LJ, Bataille D. et al. International Union of Pharmacology XXXV.The glucagon receptor family. Pharmacol Rev 2003; 55: 167-194.
- 44 Lee CQ, Yun YD, Hoeffler JP. et al. Cyclic-AMP-responsive transcriptional activation of CREB-327 involves interdependent phosphorylated subdomains. EMBO J 1990; 09: 4455-4465.
- 45 Gonzalez GA, Montminy MR. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 1989; 59: 675-680.
- 46 Montminy M, Koo SH, Zhang X. The CREB family: key regulators of hepatic metabolism. Ann Endocrinol (Paris) 2004; 65: 73-75.
- 47 Heaton JH, Nebes VL, O’Dell LG. et al. Glucocorticoid and cyclic nucleotide regulation of plasminogen activator and plasminogen activator-inhibitor gene expression in primary cultures of rat hepatocytes. Mol Endocrinol 1989; 03: 185-192.
- 48 Dimova EY, Jakubowska MM, Kietzmann T. CREB binding to the hypoxia-inducible factor-1 responsive elements in the plasminogen activator inhibitor-1 promoter mediates the glucagon effect. Thromb Haemost 2007; 98: 296-303.
- 49 Heaton JH, Gelehrter TD. Cyclic nucleotide regulation of plasminogen activator and plasminogen activator-inhibitor messenger RNAs in rat hepatoma cells. Mol Endocrinol 1990; 04: 171-178.
- 50 Heaton JH, Tillmann BM, Leff NS. et al. Cyclic nucleotide regulation of type-1 plasminogen activator-inhibitor mRNA stability in rat hepatoma cells Identification of cis-acting sequences. J Biol Chem 1998; 273: 14261-14268.
- 51 Tillmann-Bogush M, Heaton JH, Gelehrter TD. Cyclic nucleotide regulation of PAI-1 mRNA stability Identification of cytosolic proteins that interact with an a-rich sequence. J Biol Chem 1999; 274: 1172-1179.
- 52 Heaton JH, Dlakic WM, Dlakic M. et al. Identification and cDNA cloning of a novel RNA-binding protein that interacts with the cyclic nucleotide-responsive sequence in the Type-1 plasminogen activator inhibitor mRNA. J Biol Chem 2001; 276: 3341-3347.
- 53 Thoresen GH, Sand TE, Refsnes M. et al. Dual effects of glucagon and cyclic AMP on DNA synthesis in cultured rat hepatocytes: stimulatory regulation in early G1 and inhibition shortly before the S phase entry. J Cell Physiol 1990; 144: 523-530.
- 54 Diehl AM, Yang SQ, Wolfgang D. et al. Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver. J Clin Invest 1992; 89: 1706-1712.
- 55 Uno S, Nakamura M, Seki T. et al. Induction of tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) as early growth responses in rat hepatocytes in primary culture. Biochem Biophys Res Commun 1997; 239: 123-128.
- 56 Mars WM, Zarnegar R, Michalopoulos GK. Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA. Am J Pathol 1993; 143: 949-958.
- 57 Yee JA, Yan L, Dominguez JC. et al. Plasminogendependent activation of latent transforming growth factor beta (TGF beta) by growing cultures of osteoblastlike cells. J Cell Physiol 1993; 157: 528-534.
- 58 Fanelli CG, Porcellati F, Rossetti P. et al. Glucagon: the effects of its excess and deficiency on insulin action. Nutr Metab Cardiovasc Dis 2006; 16 (Suppl. 01) S28-S34.
- 59 Grant MB, Ellis EA, Caballero S. et al. Plasminogen activator inhibitor-1 overexpression in nonproliferative diabetic retinopathy. Exp Eye Res 1996; 63: 233-244.
- 60 Minneman KP, Esbenshade TA. Alpha 1-adrenergic receptor subtypes. Annu Rev Pharmacol Toxicol 1994; 34: 117-133.
- 61 Bylund DB, Regan JW, Faber JE. et al. Vascular alpha-adrenoceptors: from the gene to the human. Can J Physiol Pharmacol 1995; 73: 533-543.
- 62 Hieble JP, Bondinell WE, Ruffolo Jr RR. Alphaand beta-adrenoceptors: from the gene to the clinic1. Molecular biology and adrenoceptor subclassification. J Med Chem 1995; 38: 3415-3444.
- 63 Xing M, Post S, Ostrom RS. et al. Inhibition of phospholipase A2-mediated arachidonic acid release by cyclic AMP defines a negative feedback loop for P2Y receptor activation in Madin-Darby canine kidney D1 cells. J Biol Chem 1999; 274: 10035-10038.
- 64 Ruan Y, Kan H, Parmentier JH. et al. Alpha-1A adrenergic receptor stimulation with phenylephrine promotes arachidonic acid release by activation of phospholipase D in rat-1 fibroblasts: inhibition by protein kinase A. J Pharmacol Exp Ther 1998; 284: 576-585.
- 65 Williams NG, Zhong H, Minneman KP. Differential coupling of alpha1-, alpha2-, and beta-adrenergic receptors to mitogen-activated protein kinase pathways and differentiation in transfected PC12 cells. J Biol Chem 1998; 273: 24624-24632.
- 66 Xiao L, Pimentel DR, Wang J. et al. Role of reactive oxygen species and NAD(P)H oxidase in alpha(1)-adrenoceptor signaling in adult rat cardiac myocytes. Am J Physiol Cell Physiol 2002; 282: C926-C934.
- 67 Brown NJ, Bradford J, Wang Z. et al. Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency. Kidney Int 2007; 72: 72-81.
- 68 Garcia-Caballero A, Olivares-Reyes JA, Catt KJ. et al. Angiotensin AT(1) receptor phosphorylation and desensitization inahepatic cell line Roles of protein kinase c and phosphoinositide 3-kinase. Mol Pharmacol 2001; 59: 576-585.
- 69 Vaughan DE. Angiotensin and vascularfibrinolytic balance. Am J Hypertens 2002; 15: 3S-8S.
- 70 Wilms H, Rosenstiel P, Unger T. et al. Neuroprotection with angiotensin receptor antagonists: a review of the evidence and potential mechanisms. Am J Cardiovasc Drugs 2005; 05: 245-253.
- 71 Rockey DC. Vascular mediators in the injured liver. Hepatology 2003; 37: 4-12.
- 72 Garcia-Sainz JA, Macias-Silva M. Angiotensin II stimulates phosphoinositide turnover and phosphorylase through AII-1 receptors in isolated rat hepatocytes. Biochem Biophys Res Commun 1990; 172: 780-785.
- 73 Nakamura S, Nakamura I, Ma L. et al. Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo. Kidney Int 2000; 58: 251-259.
- 74 Motojima M, Ando T, Yoshioka T. Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor type-1 (PAI-1) gene expression in mesangial cells. Biochem J 2000; 349: 435-441.
- 75 Chen HC, Feener EP. MEK1,2 response element mediates angiotensin II-stimulated plasminogen activator inhibitor-1 promoter activation. Blood 2004; 103: 2636-2644.
- 76 Naldini L, Tamagnone L, Vigna E. et al. Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor. EMBO J 1992; 11: 4825-4833.
- 77 Bueno M, Salgado S, Beas-Zarate C. et al. Urokinase-type plasminogen activator gene therapy in liver cirrhosis is mediated by collagens gene expression down-regulation and up-regulation of MMPs, HGF and VEGF. J Gene Med 2006; 08: 1291-1299.
- 78 Shimizu M, Hara A, Okuno M. et al. Mechanism of retarded liver regeneration in plasminogen activatordeficient mice: Impaired activation of hepatocyte growth factor after Fas-mediated massive hepatic apoptosis. Hepatology 2001; 33: 569-576.
- 79 Bataller R, Sancho-Bru P, Gines P. et al. Liver fibrogenesis: a new role for the renin-angiotensin system. Antioxid Redox Signal 2005; 07: 1346-1355.
- 80 Calles EJ, Mirza SA, Sobel BE. et al. Induction of hyperinsulinemia combined with hyperglycemia and hypertriglyceridemia increases plasminogen activator inhibitor1 in blood in normal human subjects. Diabetes 1998; 47: 290-293.
- 81 Iwasaki Y, Kambayashi M, Asai M. et al. High glucose alone, as well as in combination with proinflammatory cytokines, stimulates nuclear factor kappaB-mediated transcription in hepatocytes in vitro. J Diabetes Complications 2007; 21: 56-62.
- 82 Li NX, Karin M. Is NF-kappa B the sensor of oxidative stress?. FASEB J 1999; 13: 1137-1143.
- 83 Bowie AG, O’Neill LAJ. Vitamin C inhibits NFkappa B activation byTNF via the activation of p38 mitogen-activated protein kinase. Journal of Immunology 2000; 165: 7180-7188.
- 84 Hayakawa M, Miyashita H, Sakamoto I. et al. Evidence that reactive oxygen species do not mediate NFkappa B activation. EMBO J 2003; 22: 3356-3366.
- 85 Hou B, Eren M, Painter CA. et al. Tumor necrosis factor alpha activates the human plasminogen activator inhibitor-1 gene through a distal nuclear factor kappaB site. J Biol Chem 2004; 279: 18127-18136.
- 86 Dawson SJ, Wiman B, Hamsten A. et al. The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 1993; 268: 10739-10745.
- 87 Chen YQ, Su M, Walia RR. et al. Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells. J Biol Chem 1998; 273: 8225-8231.
- 88 Du XL, Edelstein D, Rossetti L. et al. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci USA 2000; 97: 12222-12226.
- 89 Ahn JD, Morishita R, Kaneda Y. et al. Transcription factor decoy for activator protein-1 (AP-1) inhibits high glucoseand angiotensin II-induced type 1 plasminogen activator inhibitor (PAI-1) gene expression in cultured human vascular smooth muscle cells. Diabetologia 2001; 44: 713-720.
- 90 Suzuki M, Akimoto K, Hattori Y. Glucose upregulates plasminogen activator inhibitor-1 gene expression in vascular smooth muscle cells. Life Sci 2002; 72: 59-66.
- 91 Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001; 414: 799-806.
- 92 Lietzke SE, Bose S, Cronin T. et al. Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains. Mol Cell 2000; 06: 385-394.
- 93 Alessi DR, James SR, Downes CP. et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol 1997; 07: 261-269.
- 94 Alexander-Bridges M, Mukhopadhyay NK, Jhala U. et al. Growth factor-activated kinases phosphorylate IRE-ABP. Biochem Soc Trans 1992; 20: 691-693.
- 95 O’Brien RM, Granner DK. Regulation of gene expression by insulin. Biochem J 1991; 278: 609-619.
- 96 O’Brien RM, Bonovich MT, Forest CD. et al. Signal transduction convergence: phorbol esters and insulin inhibit phosphoenolpyruvate carboxykinase gene transcription through the same 10-base-pair sequence. Proc Natl Acad Sci USA 1991; 88: 6580-6584.
- 97 O’Brien RM, Streeper RS, Ayala JE. et al. Insulinregulated gene expression. Biochem Soc Trans 2001; 29: 552-558.
- 98 Schneider DJ, Sobel BE. Augmentation of synthesis of plasminogen activator inhibitor type 1 by insulin and insulin-like growth factor type I: implications for vascular disease in hyperinsulinemic states [published erratum appears in Proc Natl Acad Sci USA 1992; 89: 1148]. Proc Natl Acad Sci USA 1991; 88: 9959-9963.
- 99 Kietzmann T, Samoylenko A, Roth U. et al. Hypoxia-inducible factor-1 and hypoxia response elements mediate the induction of plasminogen activator inhibitor-1 gene expression by insulin in primary rat hepatocytes. Blood 2003; 101: 907-914.
- 100 Li XN, Grenett HE, Benza RL. et al. Genotypespecific transcriptional regulation of PAI-1 expression by hypertriglyceridemic VLDL and Lp(a) in cultured human endothelial cells. Arterioscler Thromb Vasc Biol 1997; 17: 3215-3223.
- 101 Grenett HE, Benza RL, Li XN. et al. Expression of plasminogen activator inhibitor type I in genotyped human endothelial cell cultures: genotype-specific regulation by insulin. Thromb Haemost 1999; 82: 1504-1509.
- 102 Banfi C, Eriksson P, Giandomenico G. et al. Transcriptional regulation of plasminogen activator inhibitor type 1 gene by insulin: insights into the signaling pathway. Diabetes 2001; 50: 1522-1530.
- 103 Dimova EY, Kietzmann T. The MAPK pathway and HIF-1 are involved in the induction of the human PAI-1 gene expression by insulin in the human hepatoma cell line HepG2. Ann NY Acad Sci 2006; 1090: 355-367.
- 104 Zelzer E, Levy Y, Kahana C. et al. Insulin induces transcription of target genes through the hypoxia-inducible factor HIF-1alpha/ARNT. EMBO J 1998; 17: 5085-5094.
- 105 Jiang BH, Jiang G, Zheng JZ. et al. Phosphatidylinositol 3-kinase signaling controls levels of hypoxiainducible factor 1. Cell Growth Differ 2001; 12: 363-369.
- 106 Stiehl DP, Jelkmann W, Wenger RH. et al. Normoxic induction of the hypoxia-inducible factor 1alpha by insulin and interleukin-1beta involves the phosphatidylinositol 3-kinase pathway. FEBS Lett 2002; 512: 157-162.
- 107 Treins C, Giorgetti-Peraldi S, Murdaca J. et al. Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. J Biol Chem 2002; 277: 27975-27981.
- 108 Richard DE, Berra E, Pouyssegur J. Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells. J Biol Chem 2000; 275: 26765-26771.
- 109 Gorlach A, Diebold I, Schini-Kerth VB. et al. Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells: Role of the p22(phox)-containing NADPH oxidase. Circ Res 2001; 89: 47-54.
- 110 Dimova EY, Kietzmann T. Cell type-dependent regulation of the hypoxia-responsive plasminogen activator inhibitor-1 gene by upstream stimulatory factor-2. J Biol Chem 2006; 281: 2999-3005.
- 111 Vulin AI, Stanley FM. A Forkhead/winged helixrelated transcription factor mediates insulin-increased plasminogen activator inhibitor-1 gene transcription. J Biol Chem 2002; 277: 20169-20176.
- 112 Wang D, Sul HS. Upstream stimulatory factors bind to insulin response sequence of the fatty acid synthase promoter USF1 is regulated. J Biol Chem 1995; 270: 28716-28722.
- 113 Wang D, Sul HS. Upstream stimulatory factor binding to the E-box at -65 is required for insulin regulation of the fatty acid synthase promoter. J Biol Chem 1997; 272: 26367-26374.
- 114 Shepherd PR, Nave BT, Rincon J. et al. Involvement of phosphoinositide 3-kinase in insulin stimulation of MAP-kinase and phosphorylation of protein kinase-B in human skeletal muscle: implications for glucose metabolism. Diabetologia 1997; 40: 1172-1177.
- 115 Brunet A, Bonni A, Zigmond MJ. et al. Akt promotes cell survival by phosphorylating and inhibitinga Forkhead transcription factor. Cell 1999; 96: 857-868.
- 116 Kops GJ, de Ruiter ND, Vries-Smits AM. et al. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 1999; 398: 630-634.
- 117 Rena G, Guo S, Cichy SC. et al. Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B. J Biol Chem 1999; 274: 17179-17183.
- 118 Biggs III WH, Meisenhelder J, Hunter T. et al. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA 1999; 96: 7421-7426.
- 119 Takaishi H, Konishi H, Matsuzaki H. et al. Regulation of nuclear translocation of forkhead transcription factor AFX by protein kinase B. Proc Natl Acad Sci USA 1999; 96: 11836-11841.
- 120 Grant PJ, Kruithof EK, Felley CP. et al. Short-term infusions of insulin, triacylglycerol and glucose do not cause acute increases in plasminogen activator inhibitor-1 concentrations in man. Clin Sci (Lond) 1990; 79: 513-516.
- 121 Landin K, Tengborn L, Chmielewska J. et al. The acute effect of insulin on tissue plasminogen activator and plasminogen activator inhibitor in man. Thromb Haemost 1991; 65: 130-133.
- 122 Vuorinen-Markkola H, Puhakainen I, Yki-Jarvinen H. No evidence for short-term regulation of plasminogen activator inhibitor activity by insulin in man. Thromb Haemost 1992; 67: 117-120.
- 123 Carmassi F, Morale M, Ferrini L. et al. Local insulin infusion stimulates expression of plasminogen activator inhibitor-1 and tissue-type plasminogen activator in normal subjects. Am J Med 1999; 107: 344-350.
- 124 Dimova EY, Moller U, Herzig S. et al. Transcriptional regulation of plasminogen activator inhibitor-1 expression by insulin-like growth factor-1 via MAP kinases and hypoxia-inducible factor-1 in HepG2 cells. Thromb Haemost 2005; 93: 1176-1184.
- 125 Dostert A, Heinzel T. Negative glucocorticoid receptor response elements and their role in glucocorticoid action. Curr Pharm Des 2004; 10: 2807-2816.
- 126 Gottlicher M, Heck S, Herrlich P. Transcriptional cross-talk, the second mode of steroid hormone receptor action. J Mol Med 1998; 76: 480-489.
- 127 Coombs RJ, Jenkins N. Characterization ofa plasminogen activator inhibitor induced by glucocorticoids in immature bovine Sertoli cell-enriched cultures. J Endocrinol 1988; 117: 69-74.
- 128 Loskutoff DJ, Roegner K, Erickson LA. et al. The dexamethasone-induced inhibitor of plasminogen activator in hepatoma cells is antigenically-related to an inhibitor produced by bovine aortic endothelial cells. Thromb Haemost 1986; 55: 8-11.
- 129 Bruzdzinski CJ, Johnson MR, Goble CA. et al. Mechanism of glucocorticoid induction of the rat plasminogen activator inhibitor-1 gene in HTC rat hepatoma cells: identification of cis-acting regulatory elements. Mol Endocrinol 1993; 07: 1169-1177.
- 130 Riccio A, Lund LR, Sartorio R. et al. The regulatory region of the human plasminogen activator inhibitor type-1 (PAI-1) gene. Nucleic Acids Res 1988; 16: 2805-2824.
- 131 Song CZ, Tian X, Gelehrter TD. Glucocorticoid receptor inhibits transforming growth factor-beta signaling by directly targeting the transcriptional activation function of Smad3. Proc Natl Acad Sci USA 1999; 96: 11776-11781.
- 132 Li G, Wang S, Gelehrter TD. Identification of glucocorticoid receptor domains involved in transrepression of transforming growth factor-beta action. J Biol Chem 2003; 278: 41779-41788.
- 133 Song CZ, Siok TE, Gelehrter TD. Smad4/DPC4 and Smad3 mediate transforming growth factor-beta (TGF-beta) signaling through direct binding to a novel TGF-beta-responsive element in the human plasminogen activator inhibitor-1 promoter. J Biol Chem 1998; 273: 29287-29290.
- 134 Allen RR, Qi L, Higgins PJ. Upstream stimulatory factor regulates E box-dependent PAI-1 transcription in human epidermal keratinocytes. J Cell Physiol 2005; 203: 156-165.
- 135 Kutz SM, Higgins CE, Samarakoon R. et al. TGFbeta 1-induced PAI-1 expression is E box/USF-dependent and requires EGFR signaling. Exp Cell Res 2006; 312: 1093-1105.
- 136 Li G, Heaton JH, Gelehrter TD. Role of steroid receptor coactivators in glucocorticoid and transforming growth factor beta regulation of plasminogen activator inhibitor gene expression. Mol Endocrinol 2006; 20: 1025-1034.
- 137 Dennler S, Pendaries V, Tacheau C. et al. The steroid receptor co-activator-1 (SRC-1) potentiates TGFbeta/Smad signaling: role of p300/CBP. Oncogene 2005; 24: 1936-1945.
- 138 Wickert L, Chatain N, Kruschinsky K. et al. Glucocorticoids activate TGF-beta induced PAI-1 and CTGF expression in rat hepatocytes. Comp Hepatol 2007; 06: 5.
- 139 Ma Y, Ryu JS, Dulay A. et al. Regulation of plasminogen activator inhibitor (PAI)-1 expression in a human trophoblast cell line by glucocorticoid (GC) and transforming growth factor (TGF)-beta. Placenta 2002; 23: 727-734.
- 140 Descheemaeker KA, Wyns S, Nelles L. et al. Interaction of AP-1-, AP-2-, and Sp1-like proteins with two distinct sites in the upstream regulatory region of the plasminogen activator inhibitor-1 gene mediates the phorbol 12-myristate 13-acetate response. J Biol Chem 1992; 267: 15086-15091.
- 141 Arts J, Grimbergen J, Bosma PJ. et al. Role of c-Jun and proximal phorbol 12-myristate-13-acetate(PMA)-responsive elements in the regulation of basal and PMA-stimulated plasminogen-activator inhibitor-1 gene expression in HepG2. Eur J Biochem 1996; 241: 393-402.
- 142 Guo B, Inoki K, Isono M. et al. MAPK/AP-1-dependent regulation of PAI-1 gene expression by TGFbeta in rat mesangial cells. Kidney Int 2005; 68: 972-984.
- 143 Kietzmann T, Jungermann K, Gorlach A. Regulation of the hypoxia-dependent plasminogen activator inhibitor 1 expression by MAP kinases. Thromb Haemost 2003; 89: 666-673.
- 144 Chen YQ, Su M, Walia RR. et al. Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells. J Biol Chem 1998; 273: 8225-8231.
- 145 Leithauser B, Matthias FR, Nicolai U. et al. Hemostatic abnormalities and the severity of illness in patients at the onset of clinically defined sepsis. Possible indication of the degree of endothelial cell activation? Intensive Care Med 1996; 22: 631-636.
- 146 Woodhouse PR, Meade TW, Khaw KT. Plasminogen activator inhibitor-1, the acute phase response and vitamin C. Atherosclerosis 1997; 133: 71-76.
- 147 Podor TJ, Hirsh J, Gelehrter TD. et al. Type 1 plasminogen activator inhibitor is not an acute phase reactant in ratsLack of IL-6- and hepatocyte-dependent synthesis. J Immunol 1993; 150: 225-235.
- 148 de Boer JP, Abbink JJ, Brouwer MC. et al. PAI-1 synthesis in the human hepatoma cell line HepG2 is increased by cytokines--evidence that the liver contributes to acute phase behaviour of PAI-1. Thromb Haemost 1991; 65: 181-185.
- 149 Healy AM, Gelehrter TD. Induction of plasminogen activator inhibitor-1 in HepG2 human hepatoma cells by mediators of the acute phase response. J Biol Chem 1994; 269: 19095-19100.
- 150 Seki T, Gelehrter TD. Interleukin-1 induction of type-1 plasminogen activator inhibitor (PAI-1) gene expression in the mouse hepatocyte line, AML 12. J Cell Physiol 1996; 168: 648-656.
- 151 Seki T, Healy AM, Fletcher DS. et al. IL-1beta mediates induction of hepatic type 1 plasminogen activator inhibitor in response to local tissue injury. Am J Physiol 1999; 277: G801-G809.
- 152 Dong J, Fujii S, Li H. et al. Interleukin-6 and mevastatin regulate plasminogen activator inhibitor-1 through CCAAT/enhancer-binding protein-delta. Arterioscler Thromb Vasc Biol 2005; 25: 1078-1084.
- 153 Kasza A, Kiss DL, Gopalan S. et al. Mechanism of plasminogen activator inhibitor-1 regulation by oncostatin M and interleukin-1 in human astrocytes. J Neurochem 2002; 83: 696-703.
- 154 Gruber F, Hufnagl P, Hofer-Warbinek R. et al. Direct binding of Nur77/NAK-1 to the plasminogen activator inhibitor1 (PAI-1) promoter regulates TNF alpha-induced PAI-1 expression. Blood 2003; 101: 3042-3048.
- 155 Mastrapasqua G, Scapinello A, Madia D. et al. Ischemic hepatitis Description of4 cases and review of the literature. Minerva-Gastroenterol-Dietol 1993; 39: 93-97.
- 156 Mathurin P, Durand F, Ganne N. et al. Ischemic hepatitis due to obstructive sleep apnea. Gastroenterology 1995; 109: 1682-1684.
- 157 Horie Y, Wolf R, Anderson DC. et al. Hepatic leukostasis and hypoxic stress in adhesion molecule-deficient mice after gut ischemia/reperfusion. J Clin Invest 1997; 99: 781-788.
- 158 Horie Y, Wolf R, Miyasaka M. et al. Leukocyte adhesion and hepatic microvascular responses to intestinal ischemia/reperfusion in rats. Gastroenterology 1996; 111: 666-673.
- 159 Zimmerman HJ. Hepatotoxicity. New York: Appleton-Century-Crafts; 1978
- 160 Israel Y, Orrego H. Hepatocyte demand and substrate supply as factors in the susceptibility to alcoholic liver injury: pathogenesis and prevention. Clin Gastroenterol 1981; 10: 355-373.
- 161 Lieber CS. Biochemical factors in alcoholic liver disease. Semin Liver Dis 1993; 13: 136-153.
- 162 Jauhonen P, Baraona E, Miyakawa H. et al. Mechanism for selective perivenular hepatotoxicity of ethanol. Alcohol Clin Exp Res 1982; 06: 350-357.
- 163 Baraona E, Jauhonen P, Miyakawa H. et al. Zonal redox changes as a cause of selective perivenular hepatotoxicity of alcohol. Pharmacol Biochem Behav 1983; 18 (Suppl. 01) 449-454.
- 164 Pinsky DJ, Liao H, Lawson CA. et al. Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. J Clin Invest 1998; 102: 919-928.
- 165 Kietzmann T, Roth U, Jungermann K. Induction of the plasminogen activator inhibitor-1 gene expression by mild hypoxia via a hypoxia response element binding the hypoxia inducible factor-1 in rat hepatocytes. Blood 1999; 94: 4177-4185.
- 166 Samoylenko A, Roth U, Jungermann K. et al. The upstream stimulatory factor-2a inhibits plasminogen activator inhibitor-1 gene expression by binding to a promoter element adjacent to the hypoxia-inducible factor-1 binding site. Blood 2001; 97: 2657-2666.
- 167 Fink T, Ebbesen P, Zachar V. Quantitative gene expression profiles of human liver-derived cell lines exposed to moderate hypoxia. Cell Physiol Biochem 2001; 11: 105-114.
- 168 Liao H, Hyman MC, Lawrence DA. et al. Molecular regulation of the PAI-1 gene by hypoxia: contributions of Egr-1, HIF-1alpha, and C/EBPalpha. FASEB J 2007; 21: 935-949.
- 169 Meade ES, Ma YY, Guller S. Role of hypoxia-inducible transcription factors 1alpha and 2alpha in the regulation of plasminogen activator inhibitor-1 expression in a human trophoblast cell line. Placenta 2007; 28: 1012-1019.
- 170 Carroll VA, Ashcroft M. Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res 2006; 66: 6264-6270.
- 171 Kietzmann T, Gorlach A. Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin Cell Dev Biol 2005; 16: 474-486.
- 172 Richard DE, Berra E, Gothie E. et al. p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1. J Biol Chem 1999; 274: 32631-32637.
- 173 Mylonis I, Chachami G, Samiotaki M. et al. Identification of MAPK phosphorylation sites and their role in the localization and activity of hypoxia-inducible factor-1alpha. J Biol Chem 2006; 281: 33095-33106.
- 174 Flugel D, Gorlach A, Michiels C. et al. Glycogen synthase kinase 3 phosphorylates hypoxia-inducible factor 1alpha and mediates its destabilization ina VHL-independent manner. Mol Cell Biol 2007; 27: 3253-3265.
- 175 Wang J, Yin L, Lazar MA. The orphan nuclear receptor Rev-erb alpha regulates circadian expression of plasminogen activator inhibitor type 1. J Biol Chem 2006; 281: 33842-33848.
- 176 BelAiba RS, Bonello S, Zahringer C. et al. Hypoxia up-regulates hypoxia-inducible factor-1{alpha} transcription by involving phosphatidylinositol 3-kinase and nuclear factor {kappa}B in pulmonary artery smooth muscle cells. Mol Biol Cell 2007; 18: 4691-4697.
- 177 Bonello S, Zahringer C, BelAiba RS. et al. Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site. Arterioscler Thromb Vasc Biol 2007; 27: 755-761.
- 178 Rius J, Guma M, Schachtrup C. et al. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 2008; 453: 807-811.
- 179 Tacchini L, De Ponti C, Matteucci E. et al. Hepatocyte growth factor-activated NF-kappaB regulates HIF-1 activity and ODC expression, implicated in survival, differently in different carcinoma cell lines. Carcinogenesis 2004; 25: 2089-2100.
- 180 Eckerich C, Zapf S, Fillbrandt R. et al. Hypoxia can induce c-Met expression in glioma cells and enhance SF/HGF-induced cell migration. Int J Cancer 2007; 121: 276-283.
- 181 Boccaccio C, Sabatino G, Medico E. et al. The MET oncogene drives a genetic programme linking cancer to haemostasis. Nature 2005; 434: 396-400.
- 182 Bosma PJ, van-den BE, Kooistra T. et al. Human plasminogen activator inhibitor-1 gene Promoter and structural gene nucleotide sequences. J Biol Chem 1988; 263: 9129-9141.
- 183 Bruzdzinski CJ, Riordan JM, Nordby EC. et al. Isolation and characterization of the rat plasminogen activator inhibitor-1 gene. J Biol Chem 1990; 265: 2078-2085.
- 184 Luo X, Sawadogo M. Antiproliferative properties of the USF family of helix-loop-helix transcription factors. Proc Natl Acad Sci USA 1996; 93: 1308-1313.
- 185 Ismail PM, Lu T, Sawadogo M. Loss of USF transcriptional activity in breast cancer cell lines. Oncogene 1999; 18: 5582-5591.
- 186 Qyang Y, Luo X, Lu T. et al. Cell-type-dependent activity of the ubiquitous transcription factor USF in cellular proliferation and transcriptional activation. Mol Cell Biol 1999; 19: 1508-1517.
- 187 Gross C, Dubois-Pot H, Wasylyk B. The ternary complex factor Net/Elk-3 participates in the transcriptional response to hypoxia and regulates HIF-1 alpha. Oncogene 2008; 27: 1333-1341.
- 188 Buchwalter G, Gross C, Wasylyk B. The ternary complex factor Net regulates cell migration through inhibition of PAI-1 expression. Mol Cell Biol 2005; 25: 10853-10862.