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.
Article
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| ID: wpr-104280
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WPRO
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.
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WPRIM
Asunto principal:
Butadienos
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Immunoblotting
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Células Cultivadas
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Colesterol
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Inhibidor Tisular de Metaloproteinasa-2
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Metaloproteinasa 2 de la Matriz
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Ciclodextrinas
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Quinasas MAP Reguladas por Señal Extracelular
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Proteínas Quinasas JNK Activadas por Mitógenos
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Microscopía Electrónica de Transmisión
Límite:
Child
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Child, preschool
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Humans
Idioma:
En
Revista:
Experimental & Molecular Medicine
Año:
2010
Tipo del documento:
Article