Colla Corii Asini regulate collagen regeneration in UV exposure-induced skin photoaging in mice
Yuman Ma1, Jun Huang1, Junxiao Gong1
1Experimental Research Center, China Academy of Chinese Medical Sciences, No.16, Nanxiao Street, Dongzhimen, Dongcheng District, Beijing, People's Republic of China.
Background:
Ultraviolet (UV) radiation is the primary external factor driving skin aging, mainly due to imbalanced collagen synthesis and degradation. Identifying new drugs targeting collagen regeneration may effectively delay skin aging. Colla Corii Asini (CCA), derived from donkey skin, contains abundant proteins and peptides, suggesting potential benefits against photoaging through collagen homeostasis regulation. However, its mechanisms and active components remain unclear.
Objective:
This study aimed to evaluate whether CCA mitigates photoaging by regulating collagen synthesis and degradation, identifying its active components and molecular targets to support future pharmacological studies.
Methods:
A photoaging mouse model was established, and the therapeutic effects of CCA were assessed through in vivo optical imaging and ex vivo analyses. Human dermal fibroblasts were employed to explore mechanisms of collagen regulation by CCA. PPI analysis and AlphaFold3 were used to predict and validate key active peptides and molecular targets.
Results:
CCA significantly improved the structure and appearance of photoaged skin, reduced oxidative stress and inflammation, and enhanced collagen content and density. Mass spectrometry identified 98 peptides closely linked to protein synthesis. Mechanistically, CCA increased collagen synthesis and reduced aging markers by activating the TGFβ-SMAD signaling pathway, balancing MMPs and TIMPs. Importantly, this effect is primarily associated with the core CCA peptide YYTSASGDEMVSLK binding to and upregulating TGFBR1 and TGFBR2 expression, activating the TGFβ-SMAD pathway, and promoting collagen regeneration.
Conclusion:
CCA, particularly peptide YYTSASGDEMVSLK, has potential to slow skin photoaging, highlighting a promising therapeutic strategy for skin aging management.
Insights
Colla Corii Asini (CCA) effectively combats skin photoaging by boosting collagen production and reducing inflammation. Its peptide YYTSASGDEMVSLK activates key pathways, offering a promising therapeutic for skin aging.
Area of Science:
- Dermatology
- Biochemistry
- Pharmacology
Background:
- Ultraviolet (UV) radiation is a primary driver of skin aging, causing collagen imbalance.
- Colla Corii Asini (CCA), from donkey skin, shows potential for photoaging treatment but lacks clear mechanisms.
- Research is needed to identify CCA's active components and their role in collagen homeostasis.
Purpose of the Study:
- Evaluate CCA's efficacy in mitigating UV-induced skin aging.
- Investigate CCA's effects on collagen synthesis and degradation pathways.
- Identify active peptides and molecular targets of CCA for pharmacological applications.
Main Methods:
- Established a photoaging mouse model for in vivo assessment.
- Utilized optical imaging and ex vivo analyses to evaluate CCA's effects.
- Employed human dermal fibroblasts, mass spectrometry, PPI analysis, and AlphaFold3 for mechanistic and component identification.
Main Results:
- CCA significantly improved skin structure, reduced oxidative stress, and increased collagen density.
- Identified 98 peptides in CCA, with YYTSASGDEMVSLK linked to collagen regeneration.
- CCA activates the TGFβ-SMAD pathway by upregulating TGFBR1/2, promoting collagen synthesis and balancing MMPs/TIMPs.
Conclusions:
- CCA demonstrates significant therapeutic potential for managing skin photoaging.
- The peptide YYTSASGDEMVSLK is identified as a key component driving CCA's anti-aging effects.
- CCA represents a promising strategy for developing new treatments for skin aging.
