Reactive site-dependent phenotypic alterations in plasminogen activator inhibitor-1 transgenic mice.
J Thromb Haemost
; 5(7): 1500-8, 2007 Jul.
Article
em En
| MEDLINE
| ID: mdl-17439629
ABSTRACT
BACKGROUND:
Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of plasminogen activators (PAs) and plays a role in the regulation of a number of physiological processes including the degradation of extracellular matrix proteins, cell proliferation and migration, and intracellular signaling.AIM:
To characterize the effects of durable expression of a stable form of human PAI-1 and to characterize important structure-function relationships in PAI-1 in vivo.METHODS:
We developed transgenic mice lines overexpressing stable variants of human PAI-1 under the control of the murine preproendothelin-1 promoter and characterized the phenotypic alterations displayed by transgenic mice.RESULTS:
Transgenic mice expressing an active form of human PAI-1 (PAI-1-stab) display complex phenotypic abnormalities including alopecia and hepatosplenomegaly. Reactive site mutant transgenic mice expressing inactive PAI-1 exhibit complete phenotypic rescue, while transgenic mice expressing PAI-1 with reduced affinity for vitronectin manifest all of the phenotypic abnormalities present in PAI-1-stab transgenic mice.CONCLUSIONS:
The protease inhibitory activity of PAI-1 toward PAs and/or other serine proteases is necessary and sufficient to promote complex phenotypic abnormalities and mediates many of the physiological effects of PAI-1 in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidor 1 de Ativador de Plasminogênio
Limite:
Animals
Idioma:
En
Revista:
J Thromb Haemost
Ano de publicação:
2007
Tipo de documento:
Article