title: Methyl-β-cyclodextrin up-regulates collagen I expression in chronologically-aged skin via its anti-caveolin-1 activity.
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.
authors.affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Da-In
authors.initials: DI
authors.lastname: Choi
authors.affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Urology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Sun-Ok
authors.initials: SO
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Cho
authors.affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jee-Bum
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Sook-Jung
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D051242:Caveolin 1; D024042:Collagen Type I; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin