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
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Butadienes
/
Immunoblotting
/
Cells, Cultured
/
Cholesterol
/
Tissue Inhibitor of Metalloproteinase-2
/
Matrix Metalloproteinase 2
/
Cyclodextrins
/
Extracellular Signal-Regulated MAP Kinases
/
JNK Mitogen-Activated Protein Kinases
/
Microscopy, Electron, Transmission
Limits:
Child
/
Child, preschool
/
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2010
Type:
Article
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