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Cholesterol, a Major Component of Caveolae, Down-regulates Matrix Metalloproteinase-1 Expression through ERK/JNK Pathway in Cultured Human Dermal Fibroblasts

Cited 13 time in Web of Science Cited 14 time in Scopus
Authors
Kim, Sangmin; Han, Jeonghun; Lee, Dong Hun; Cho, Kwang Hyun; Chung, Jin Ho; Kim, Kyu Han
Issue Date
2010-11
Publisher
KOREAN DERMATOLOGICAL ASSOC
Citation
ANNALS OF DERMATOLOGY; Vol.22, no.4; 379-388
Keywords
AP-1MMP-1CholesterolMethyl-beta-cyclodextrin
Abstract
Background: Cholesterol is a major component of specialized membrane microdomains known as lipid rafts or caveolae, which modulate the fluidity of biological membranes. Membrane cholesterol therefore plays an important role in cell signaling and vesicular transport. Objective: In this study, we investigated the effects of cholesterol on matrix metalloproteinase-1 (MMP-1) expression in human dermal fibroblasts. Methods: MMP-1 mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. AP-1 DNA binding activity was detected by electrophoretic mobility shift assays. The amount of cholesterol was analyzed by cholesterol assay kit. Results: We observed that MMP-1 mRNA and protein expression was dose-dependently decreased by cholesterol treatment. In contrast, cholesterol depletion by a cholesterol depletion agent, methyl-beta-cyclodextrin (M beta CD) in human dermal fibroblasts, increased MMP-1 mRNA and protein expression in a dose-dependent manner. Also, we investigated the regulatory mechanism of M beta CD-induced MMP-1 expression: cholesterol depletion by M beta CD, activated ERK1/2 and JNK, but not p38 MAPK cascade, and it also significantly increased c-Jun phosphorylation, c-Fos expression and activator protein-1 binding activity. Furthermore, the inhibition of ERK or JNK with specific chemical inhibitors prevented M beta CD-induced MMP-1 expression, which indicates that ERK and JNK play an important role in cholesterol depletion-mediated MMP-1 induction. In addition, M beta CD-induced phosphorylation of ERK and JNK and MMP-1 expression were suppressed by cholesterol repletion. Conclusion: Our results suggest that cholesterol regulates MMP-1 expression through the control of ERK and JNK activity in human dermal fibroblasts.
ISSN
1013-9087
Language
English
URI
http://hdl.handle.net/10371/78286
DOI
https://doi.org/10.5021/ad.2010.22.4.379
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College of Medicine/School of Medicine (의과대학/대학원)Dermatology (피부과학전공)Journal Papers (저널논문_피부과학전공)
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