Cholesterol inhibits MMP-9 expression in human epidermal keratinocytes and HaCaT cells.
Cholesterol is a major component of skin lipids and acts as a regulator of vesicular trafficking and signal transduction. However, the function of cholesterol on matrix metalloproteinases (MMPs) expression of human skin is not fully understood. Here, we investigated the effects of cholesterol on MMP-9 expression in normal human keratinocytes (NHK) and HaCaT cells. Basal level of MMP-9 expression was decreased by cholesterol in NHK. On the other hand, MMP-9 expression was increased by the cholesterol depletion agent, methyl-beta-cyclodextrin (MbetaCD), while it was inhibited by cholesterol repletion in HaCaT cells. MbetaCD induced ERK and JNK phosphorylation were prevented by cholesterol repletion. The inhibition of ERK and JNK decreased MbetaCD-induced MMP-9 expression. Therefore, our results suggest that cholesterol regulates MMP-9 expression through ERK and JNK-dependent pathways.
Kim
Sangmin
S
Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
Kim
Yoonkyung
Y
Lee
Youngae
Y
Cho
Kwang Hyun
KH
Kim
Kyu Han
KH
Chung
Jin Ho
JH
D018929:Cell Culture Techniques; D002460:Cell Line; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D000078404:Epidermal Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D012867:Skin / Q000166:cytology; D013778:Tetrazolium Salts / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology
D005562:Formazans; D061965:Matrix Metalloproteinase Inhibitors; D013778:Tetrazolium Salts; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C079782:MTT formazan; D002784:Cholesterol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9