Regulation of PAI-1 gene expression during adipogenesis.
J Cell Biochem
; 101(2): 369-80, 2007 May 15.
Article
em En
| MEDLINE
| ID: mdl-17230448
ABSTRACT
Obesity is characterized by elevated levels of circulating plasminogen activator inhibitor-1 (PAI-1), which contribute towards the development of secondary disorders such as type 2 diabetes mellitus and cardiovascular complications. This increase in plasma PAI-1 levels is attributed to an increase in PAI-1 derived from adipose tissue. This study shows that adipose tissue evolved into a major PAI-1 producing organ by gaining capacity during adipocyte differentiation to respond to inducers of PAI-1 transcription. This is mediated by a decrease in E2F1 protein levels, an increase in pRB levels and a decrease in pRB phosphorylation, all leading to a decrease in levels of free E2F, a known transcriptional repressor of PAI-1. Depletion of E2F1-3 was sufficient for inducers such as insulin to potently induce PAI-1 gene expression in pre-adipocytes. Conversely, forced release of pRB-bound endogenous E2F using cell-penetrating peptides can suppress PAI-1 gene expression in adipocytes. This study describes the novel paradigm of cellular differentiation-associated increase in PAI-1 gene expression which is mediated by a decrease in repressor activity, and describes a way of desensitising terminally differentiated cells to PAI-1 inducing agents by restoring endogenous repressor activity.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Serina Proteinase
/
Regulação da Expressão Gênica
/
Inibidor 1 de Ativador de Plasminogênio
/
Adipogenia
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article