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

Lee JA, Choi DI, Choi JY, Kim SO, Cho KA, Lee JB, Yun SJ, Lee SC - Oncotarget (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.

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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MβCD-induced up-regulation of COL I is maintained for several months in mouse skinAfter last injection of 2.5% MβCD injection for 2 months, Cav-1 and COL I expression levels in the skin of hairless mice (2.5% MβCD, 2 Mo, n=3) were checked by (A) RT-PCR and (B) real-time PCR. Also, Cav-1 and COL I levels were checked at time-lapse of 2 months (2 Mo after MβCD, n=3) and 4 months (4 Mo after MβCD, n=3) after the last injection of 2.5% MβCD, respectively. Statistical significance was analyzed using a one-way ANOVA, followed by post-hoc comparisons of group means using Tukey's test. *P < 0.05, **P < 0.01. N.S.: no significant difference. Control indicates the saline-injected mice, instead of 2.5% MβCD.
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Figure 7: MβCD-induced up-regulation of COL I is maintained for several months in mouse skinAfter last injection of 2.5% MβCD injection for 2 months, Cav-1 and COL I expression levels in the skin of hairless mice (2.5% MβCD, 2 Mo, n=3) were checked by (A) RT-PCR and (B) real-time PCR. Also, Cav-1 and COL I levels were checked at time-lapse of 2 months (2 Mo after MβCD, n=3) and 4 months (4 Mo after MβCD, n=3) after the last injection of 2.5% MβCD, respectively. Statistical significance was analyzed using a one-way ANOVA, followed by post-hoc comparisons of group means using Tukey's test. *P < 0.05, **P < 0.01. N.S.: no significant difference. Control indicates the saline-injected mice, instead of 2.5% MβCD.

Mentions: From the above results, MβCD can be developed a novel anti-aging agent by up-regulating COL I level in chronologically-aged skin. Thus, we tested the durability of COL I-up-regulating activity as well as the possibility of irreversible skin fibrosis, in MβCD-injected skin. To test the durability of COL I-up-regulating activity of MβCD, 2.5% MβCD was intra-dermally injected twice-weekly into mouse skin (n=3) for two months, and the mice were kept for another two and four months after the last injection. RT-PCR/real-time PCR demonstrated that down-regulated Cav-1 expression as well as up-regulated COL I expression were induced by MβCD injection for two months. The MβCD-modulated Cav-1 and COL I expressions were also observed at two months after the last injection, but became less prominent as time lapsed after the last injection, ruling out the possibility of irreversible skin fibrosis (Figures 7A and B).


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

Lee JA, Choi DI, Choi JY, Kim SO, Cho KA, Lee JB, Yun SJ, Lee SC - Oncotarget (2015)

MβCD-induced up-regulation of COL I is maintained for several months in mouse skinAfter last injection of 2.5% MβCD injection for 2 months, Cav-1 and COL I expression levels in the skin of hairless mice (2.5% MβCD, 2 Mo, n=3) were checked by (A) RT-PCR and (B) real-time PCR. Also, Cav-1 and COL I levels were checked at time-lapse of 2 months (2 Mo after MβCD, n=3) and 4 months (4 Mo after MβCD, n=3) after the last injection of 2.5% MβCD, respectively. Statistical significance was analyzed using a one-way ANOVA, followed by post-hoc comparisons of group means using Tukey's test. *P < 0.05, **P < 0.01. N.S.: no significant difference. Control indicates the saline-injected mice, instead of 2.5% MβCD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385827&req=5

Figure 7: MβCD-induced up-regulation of COL I is maintained for several months in mouse skinAfter last injection of 2.5% MβCD injection for 2 months, Cav-1 and COL I expression levels in the skin of hairless mice (2.5% MβCD, 2 Mo, n=3) were checked by (A) RT-PCR and (B) real-time PCR. Also, Cav-1 and COL I levels were checked at time-lapse of 2 months (2 Mo after MβCD, n=3) and 4 months (4 Mo after MβCD, n=3) after the last injection of 2.5% MβCD, respectively. Statistical significance was analyzed using a one-way ANOVA, followed by post-hoc comparisons of group means using Tukey's test. *P < 0.05, **P < 0.01. N.S.: no significant difference. Control indicates the saline-injected mice, instead of 2.5% MβCD.
Mentions: From the above results, MβCD can be developed a novel anti-aging agent by up-regulating COL I level in chronologically-aged skin. Thus, we tested the durability of COL I-up-regulating activity as well as the possibility of irreversible skin fibrosis, in MβCD-injected skin. To test the durability of COL I-up-regulating activity of MβCD, 2.5% MβCD was intra-dermally injected twice-weekly into mouse skin (n=3) for two months, and the mice were kept for another two and four months after the last injection. RT-PCR/real-time PCR demonstrated that down-regulated Cav-1 expression as well as up-regulated COL I expression were induced by MβCD injection for two months. The MβCD-modulated Cav-1 and COL I expressions were also observed at two months after the last injection, but became less prominent as time lapsed after the last injection, ruling out the possibility of irreversible skin fibrosis (Figures 7A and B).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Chonnam National University Medical School, Gwangju, Korea.

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.

Show MeSH
Related in: MedlinePlus