Skin photoaging, primarily induced by the sun’s ultraviolet A (UVA) radiation, accounts for a significant portion (up to 80%) of skin aging. UVA rays penetrate deeply into the skin, causing damage such as reduced elasticity, loss of firmness, wrinkles, and pigmentation changes by damaging DNA and promoting collagen breakdown. Specifically, UVA exposure inhibits collagen synthesis by dermal cells and upregulates the production of matrix metalloproteinases (MMPs), leading to collagen degradation and the destruction of the skin’s support structure. To address this critical issue, the study by He et al. investigated the potential of recombinant type XVII collagen as a protective strategy against UVA-induced skin aging. Type XVII collagen (COL17) is a crucial transmembrane protein in the basement membrane, essential for maintaining the structural integrity of the epidermis and playing a role in skin anti-aging processes. Given that COL17 levels are reduced during aging and photoaging, and considering its documented roles in epidermal thickness, barrier function, and the promotion of type IV collagen and other basement membrane proteins, recombinant COL17 was considered as a promising candidate to counteract UVA-induced damage and enhance collagen secretion. This research aimed to explore the effects of recombinant type XVII collagen on UVA-induced skin aging and elucidate its molecular mechanisms, providing a theoretical foundation for precise treatments and prevention of photoaging.
Methods:
The researchers established a photoaging model using HaCaT cells, exposing them to an optimal dose of UVA radiation (20 J/cm2 for 25 minutes) that significantly reduced COL17 levels without causing significant cytotoxicity. Subsequently, these UVA-irradiated cells were treated with varying concentrations of recombinant COL17 (0.25, 0.5, and 1.0 mg/mL) for 24 hours. The study then evaluated the expression levels of collagen-related proteins and genes using western blot analysis and real-time quantitative polymerase chain reaction (RT-qPCR). Immunofluorescent staining was employed to assess collagen secretion and basement membrane protein expression.
Key Findings:
•Recombinant COL17 counteracted the UVA-induced decline in key basement membrane proteins by significantly boosting the production of type IV and type XVII collagen, laminin alpha 5, and integrin β1.
•It reversed the imbalance between MMPs and TIMPs induced by UVA radiation, leading to matrix metalloproteinase (MMP) downregulation (specifically MMP2, MMP3, and MMP9) and tissue inhibitor of metalloproteinase (TIMP) upregulation (TIMP1 and TIMP2).
•Recombinant COL17 activated the TGF-β/Smad signaling pathway in UVA-irradiated HaCaT cells by dose-dependently increasing the levels of TGF-β, Smad4, and phosphorylated Smad2/3, while decreasing the level of Smad7, an inhibitor of this pathway.
•It inhibited the EGFR/MAPK/AP-1 signaling pathway by concentration-dependently reducing the phosphorylation of EGFR and ERBB2, as well as downstream proteins including RAS, RAF, ERK1/2, JNK, p38, c-Fos, and c-Jun, which are known to promote MMP expression.
This study provides compelling evidence for the anti-photoaging effects of recombinant type XVII collagen in a UVA-irradiated HaCaT cell model. The novelty of this research lies in its comprehensive investigation into the molecular mechanisms by which recombinant COL17 ameliorates UVA-induced damage. The findings demonstrate that recombinant COL17 exerts its protective effects by simultaneously inhibiting the EGFR/MAPK/AP-1 signaling pathway, which reduces MMP secretion and collagen degradation, and by activating the TGF-β/Smad signaling pathway, which enhances collagen synthesis and basement membrane protein expression. Furthermore, it restores the balance of MMPs and their inhibitors, TIMPs. These results suggest that recombinant COL17 holds significant potential as an active ingredient in future anti-aging skincare formulations. Future research should focus on validating these findings in in vivo models, such as UVA-induced skin damage in hairless mice, and in clinical trials to evaluate its therapeutic efficacy against photodamage from both UVA and UVB exposure. Exploring the synergistic effects of combining recombinant COL17 with other bioactive agents could further enhance its anti-aging properties, paving the way for innovative and advanced skincare solutions.
Link to the study: https://www.mdpi.com/2079-9284/12/2/59
