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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.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.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.

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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Related in: MedlinePlus

Cav-1 expression is negatively related with COL I expression in chronologically-aged human and mouse skinTo compare the age-dependent change of Cav-1 and COL I, skin tissues were excised from the young humans (Y, n=4) and more elderly persons (O, n=4). (A) RT-PCR, (B) real time-PCR, and (C) Western blot analysis followed by densitometric analysis (D) of Cav-1 and COL I proteins in the skin was performed. Next, age-dependent changes of mRNA levels checked by (E) RT-PCR and (F) real-time PCR, and protein levels checked by (G) Western blot analysis followed by densitometric analysis (H) of Cav-1 and COL I proteins were also studied in hairless mice from different age-groups of 6-months-old (6 Mo), 12-months-old (12 Mo), and 18-months-old (18 Mo), respectively (n=4 for each age group). Statistical significance between age groups was analyzed using a t-test for human and a one-way ANOVA for mouse, respectively. *P < 0.05, **P < 0.01. N.S.: no significant difference.
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Figure 1: Cav-1 expression is negatively related with COL I expression in chronologically-aged human and mouse skinTo compare the age-dependent change of Cav-1 and COL I, skin tissues were excised from the young humans (Y, n=4) and more elderly persons (O, n=4). (A) RT-PCR, (B) real time-PCR, and (C) Western blot analysis followed by densitometric analysis (D) of Cav-1 and COL I proteins in the skin was performed. Next, age-dependent changes of mRNA levels checked by (E) RT-PCR and (F) real-time PCR, and protein levels checked by (G) Western blot analysis followed by densitometric analysis (H) of Cav-1 and COL I proteins were also studied in hairless mice from different age-groups of 6-months-old (6 Mo), 12-months-old (12 Mo), and 18-months-old (18 Mo), respectively (n=4 for each age group). Statistical significance between age groups was analyzed using a t-test for human and a one-way ANOVA for mouse, respectively. *P < 0.05, **P < 0.01. N.S.: no significant difference.

Mentions: To unravel the age-related changes in Cav-1 and collagen levels in the skin, we compared the expression levels of Cav-1 and COL I in the human skin from young- and old-aged groups. To quantify the relative mRNA levels of Cav-1 and COL I, RT-PCR and real-time PCR (RT-PCR/real-time PCR) were performed with the same samples. Western blot analyses could detect two chains of COL I protein bands (α1 and α2 chains). Depending on experimental conditions, 3rd band could be detected as a partial degradation product of COL I. In RT-PCR/real-time PCR and Western blot analyses, Cav-1 was up-regulated, but COL I was down-regulated, in the old-aged group (n=4) compared to the young-aged group (n=4) with statistical significance (Figure 1A-D). These age-dependent changes in Cav-1 and COL I levels in humans prompted a comparison of the levels in skin from mice 6-, 12-, and 18-months-of-age (n=4 for each age group), respectively. The RT-PCR/real-time PCR and Western blot analyses revealed up-regulation of Cav-1 and down-regulation of COL I in skin from 12- and 18-month-old mice, with the changes being more pronounced (but not significantly different) in the latter (Figure 1E-H).


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)

Cav-1 expression is negatively related with COL I expression in chronologically-aged human and mouse skinTo compare the age-dependent change of Cav-1 and COL I, skin tissues were excised from the young humans (Y, n=4) and more elderly persons (O, n=4). (A) RT-PCR, (B) real time-PCR, and (C) Western blot analysis followed by densitometric analysis (D) of Cav-1 and COL I proteins in the skin was performed. Next, age-dependent changes of mRNA levels checked by (E) RT-PCR and (F) real-time PCR, and protein levels checked by (G) Western blot analysis followed by densitometric analysis (H) of Cav-1 and COL I proteins were also studied in hairless mice from different age-groups of 6-months-old (6 Mo), 12-months-old (12 Mo), and 18-months-old (18 Mo), respectively (n=4 for each age group). Statistical significance between age groups was analyzed using a t-test for human and a one-way ANOVA for mouse, respectively. *P < 0.05, **P < 0.01. N.S.: no significant difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Cav-1 expression is negatively related with COL I expression in chronologically-aged human and mouse skinTo compare the age-dependent change of Cav-1 and COL I, skin tissues were excised from the young humans (Y, n=4) and more elderly persons (O, n=4). (A) RT-PCR, (B) real time-PCR, and (C) Western blot analysis followed by densitometric analysis (D) of Cav-1 and COL I proteins in the skin was performed. Next, age-dependent changes of mRNA levels checked by (E) RT-PCR and (F) real-time PCR, and protein levels checked by (G) Western blot analysis followed by densitometric analysis (H) of Cav-1 and COL I proteins were also studied in hairless mice from different age-groups of 6-months-old (6 Mo), 12-months-old (12 Mo), and 18-months-old (18 Mo), respectively (n=4 for each age group). Statistical significance between age groups was analyzed using a t-test for human and a one-way ANOVA for mouse, respectively. *P < 0.05, **P < 0.01. N.S.: no significant difference.
Mentions: To unravel the age-related changes in Cav-1 and collagen levels in the skin, we compared the expression levels of Cav-1 and COL I in the human skin from young- and old-aged groups. To quantify the relative mRNA levels of Cav-1 and COL I, RT-PCR and real-time PCR (RT-PCR/real-time PCR) were performed with the same samples. Western blot analyses could detect two chains of COL I protein bands (α1 and α2 chains). Depending on experimental conditions, 3rd band could be detected as a partial degradation product of COL I. In RT-PCR/real-time PCR and Western blot analyses, Cav-1 was up-regulated, but COL I was down-regulated, in the old-aged group (n=4) compared to the young-aged group (n=4) with statistical significance (Figure 1A-D). These age-dependent changes in Cav-1 and COL I levels in humans prompted a comparison of the levels in skin from mice 6-, 12-, and 18-months-of-age (n=4 for each age group), respectively. The RT-PCR/real-time PCR and Western blot analyses revealed up-regulation of Cav-1 and down-regulation of COL I in skin from 12- and 18-month-old mice, with the changes being more pronounced (but not significantly different) in the latter (Figure 1E-H).

Bottom Line: Caveolin-1 (Cav-1) is one of the key molecules to modulate collagen metabolism in the skin.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.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.

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