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.
Highlights
Caveolins are principal integral membrane proteins of caveolae, which comprise at least four proteins – caveolin-1α, 1β (21–24 kDa), and -2 (20 kDa) – that are co-expressed to form hetero-oligomeric complex in many cells, whereas caveolin-3 (18 kDa) is muscle specific [13]
This study demonstrates that decreased collagen I (COL I) level in chronologically-aged skin is closely related with elevated Cav-1 level
There was a negative correlation between expression levels of Cav-1 and COL I in chronologically-aged human and mouse skin in vivo
Summary
Caveolins are principal integral membrane proteins of caveolae, which comprise at least four proteins – caveolin-1α, 1β (21–24 kDa), and -2 (20 kDa) – that are co-expressed to form hetero-oligomeric complex in many cells, whereas caveolin-3 (18 kDa) is muscle specific [13] Besides their structural role, caveolins have a gatekeeping role in modulating various signaling molecules localized to the membrane component [4, 5]. Cav-1 was reported to exert an inhibitory activity by modulating transforming growth factor- β (TGF-β) signaling through its participation in TGF-β receptor (TβR) internalization [10] These studies suggest that Cav-1 plays a brake role in collagen expression in the skin or DFs. In contrast, Cav-1 was reported to play an accelerator role by up-regulating collagen I (COL I) via the TGF-β pathway in DFs or Cav-1 transgenic mice [13, 14]. In relation with skin aging, reduced www.impactjournals.com/oncotarget
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