Induction of tissue inhibitor of matrix metalloproteinase-2 by cholesterol depletion leads to the conversion of proMMP-2 into active MMP-2 in human dermal fibroblasts
Experimental & Molecular Medicine
;
: 38-46, 2010.
Artigo
em Inglês
| WPRIM
| ID: wpr-104280
ABSTRACT
Cholesterol is one of major components of cell membrane and plays a role in vesicular trafficking and cellular signaling. We investigated the effects of cholesterol on matrix metalloproteinase-2 (MMP-2) activation in human dermal fibroblasts. We found that tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression and active form MMP-2 (64 kD) were dose-dependently increased by methyl-beta-cyclodextrin (MbetaCD), a cholesterol depletion agent. In contrast, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation were suppressed by cholesterol repletion. Then we investigated the regulatory mechanism of TIMP-2 expression by cholesterol depletion. We found that the phosphorylation of JNK as well as ERK was significantly increased by cholesterol depletion. Moreover, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation was significantly decreased by MEK inhibitor U0126, and JNK inhibitor SP600125, respectively. While a low dose of recombinant TIMP-2 (100 ng/ml) increased the level of active MMP-2 (64 kD), the high dose of TIMP-2 (> or = 200 ng/ml) decreased the level of active MMP-2 (64 kD). Taken together, we suggest that the induction of TIMP-2 by cholesterol depletion leads to the conversion of proMMP-2 (72 kD) into active MMP-2 (64 kD) in human dermal fibroblasts.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Butadienos
/
Immunoblotting
/
Células Cultivadas
/
Colesterol
/
Inibidor Tecidual de Metaloproteinase-2
/
Metaloproteinase 2 da Matriz
/
Ciclodextrinas
/
MAP Quinases Reguladas por Sinal Extracelular
/
Proteínas Quinases JNK Ativadas por Mitógeno
/
Microscopia Eletrônica de Transmissão
Limite:
Criança
/
Criança, pré-escolar
/
Humanos
Idioma:
Inglês
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2010
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS