Journal
ONCOTARGET
Volume 6, Issue 4, Pages 1942-1953Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3039
Keywords
Anti-aging; Caveolin-1; Collagen I; Methyl-beta-cyclodextrin
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2012R1A2A2A01014695]
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Caveolin-1 (Cav-1) is one of the key molecules to modulate collagen metabolism in the skin. This study aimed to unravel the relationship between Cav-1 and collagen levels in the aged skin, and also to evaluate a new role of anti-Cav-1 agent as a collagen-modulating agent. A negative correlation between Cav-1 and collagen I (COL I) was detected in chronologically aged skin of humans and mice, which was further confirmed by Cav-1 knock-down or knock-out experiments. Next, we tested whether methyl-beta-cyclodextrin (M beta CD) as a chemical Cav-1 inhibitor could be developed as a collagen-modulating agent in the skin. Testing different conditions of M beta CD injection via the intra-dermal route revealed that 2.5% M beta CD administered twice per week for two months showed a potent COL I-up-regulating activity, leading to the increase of skin thickness (P < 0.05) without adverse reactions such as skin fibrosis. In human dermal fibroblasts, M beta CD treatment induced up-regulated COL I and down-regulated Cav-1, supporting the results of mouse experiments. Collectively, M beta CD has a COL I-enhancing activity in chronologically-aged skin, where Cav-1 acts as a brake in COL I expression, suggesting its potential role for an anti-aging agent.
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