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
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Butadiènes
/
Immunotransfert
/
Cellules cultivées
/
Cholestérol
/
Inhibiteur tissulaire de métalloprotéinase-2
/
Matrix metalloproteinase 2
/
Cyclodextrines
/
Extracellular Signal-Regulated MAP Kinases
/
JNK Mitogen-Activated Protein Kinases
/
Microscopie électronique à transmission
Limites du sujet:
Enfant
/
Enfant d'âge préscolaire
/
Humains
langue:
Anglais
Texte intégral:
Experimental & Molecular Medicine
Année:
2010
Type:
Article
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS