Down-regulation of tissue inhibitor of metalloproteinase-3 (TIMP-3) expression is necessary for adipocyte differentiation.
J Biol Chem
; 285(9): 6508-14, 2010 Feb 26.
Article
em En
| MEDLINE
| ID: mdl-20056610
ABSTRACT
Matrix metalloproteinase activity is essential for proper extracellular matrix remodeling that takes place during adipose tissue formation. Four tissue inhibitors of matrix metalloproteinases (TIMPs) regulate their activity. However, the role of TIMPs in adipocyte differentiation is poorly understood. We found that the expression of all TIMPs was modified during adipocyte differentiation, but that of TIMP-3 was distinguished by its extreme down-regulation. TIMP-3 expression was closely linked to the differentiation process. Indeed, it remained low during the adipocyte differentiation but increased when cell differentiation was prevented. We identified the transcription factor Sp1 as being responsible for the regulation of TIMP-3 expression during adipocyte differentiation. Overexpression of TIMP-3 reduced adipocyte differentiation, underlining its active role in this process. TIMP-3 overexpression decreased the expression of the early and obligate key inductors of adipogenesis Krüppel-like factor 4 (Klf4), early growth response 2 (Egr2/Krox20), and CAAT/enhancer-binding protein beta (C/EBPbeta). Our results indicate that during preadipocyte differentiation, the Sp1-dependent decrease in TIMP-3 expression is required for the successful implementation of the adipocyte differentiation program.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
/
Diferenciação Celular
/
Fator de Transcrição Sp1
/
Adipócitos
/
Inibidor Tecidual de Metaloproteinase-3
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França