Metabolic, hormonal and environmental regulation of plasminogen activator inhibitor-1 (PAI-1) expression: lessons from the liver.
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 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 over-expression 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 for a 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.
Dimova
Elitsa Y
EY
Department Chemistry/Biochemistry, University of Kaiserslautern, Kaiserslautern, Germany.
Kietzmann
Thomas
T
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002395:Catecholamines / Q000378:metabolism; D015687:Cell Hypoxia; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004734:Energy Metabolism; D004777:Environment; D005342:Fibrinolysis; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D002395:Catecholamines; D016207:Cytokines; D005938:Glucocorticoids; D006728:Hormones; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose