Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Methyl-β-cyclodextrin up-regulates collagen I expression in chronologically-aged skin via its anti-caveolin-1 activity

Jung-Ae Lee, Da-In Choi, Jee-Young Choi, Sun-Ok Kim, Kyung-A Cho, Jee-Bum Lee, Sook-Jung Yun and Seung-Chul Lee _

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Oncotarget. 2015; 6:1942-1953. https://doi.org/10.18632/oncotarget.3039

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Abstract

Jung-Ae Lee1, Da-In Choi1, Jee-Young Choi1, Sun-Ok Kim2, Kyung-A Cho3, Jee-Bum Lee1, Sook-Jung Yun1 and Seung-Chul Lee1

1 Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea

2 Department of Urology, Chonnam National University Medical School, Gwangju, Korea

3 Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea

Correspondence:

Seung-Chul Lee, email:

Keywords: Anti-aging, Caveolin-1, Collagen I, Methyl-β-cyclodextrin

Abbreviations: Cav-1: caveolin-1, COL I: collagen I, HDFs: human dermal fibroblasts, MβCD: Methyl-β-cyclodextrin

Received: October 06, 2014 Accepted: December 09, 2014 Published: December 10, 2014

Abstract

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-β-cyclodextrin (MβCD) as a chemical Cav-1 inhibitor could be developed as a collagen-modulating agent in the skin. Testing different conditions of MβCD injection via the intra-dermal route revealed that 2.5% MβCD 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, MβCD treatment induced up-regulated COL I and down-regulated Cav-1, supporting the results of mouse experiments. Collectively, MβCD 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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