Synergistic Effects of Intense Pulsed Light and Glycolic Acid on Photoaging and the Involvement of CD26 in
Peihong Sun1,2, Dongxin Shi3, Ming Cheng1
1NHC Key Laboratory of Immunodermatology, Ministry of Education Key Laboratory of Immunodermatology, National Joint Engineering Research Center for Diagnosis and Treatment of Immunologic Skin Diseases, The First Hospital of China Medical University, Shenyang, China.
Background:
Intense pulsed light (IPL) and glycolic acid peels (GLY) are widely utilized treatments for photoaging. However, their combined effects and underlying mechanisms remain insufficiently studied. Notably, CD26, a critical marker in fibroblast function and collagen synthesis, has yet to be investigated in the context of photoaging.
Objectives:
Evaluating the clinical effectiveness and safety of combined IPL and GLY (IAG) treatments compared with the GLY treatment of photoaging, and investigating the role of CD26 in photoaging.
Methods:
We designed a split-faced, prospective study and recruited 20 photoaged subjects. Each facial area was randomly assigned to undergo treatment with either the IAG group or IPL group alone. Before treatment, the Alexiades Comprehensive scale was applied to assess the manifestations of photoaged skin. A total of six treatment sessions were conducted at 1-month intervals. VISIA photography and skin score were performed before each treatment session and 1 month after the final session to evaluate clinical treatment effects. Wrinkle score and histological evaluations were also conducted in UVA-induced photoaging model in C57/BL6 mice treated with three different procedures (IAG, IPL alone, and GLY alone). Additionally, western blot analysis was used to assess the expression levels of CD26 on the mouse model. A UVA-induced photoaging model was further constructed using primary human dermal fibroblasts (HDFs). Cellular aging was evaluated through β-galactosidase (SA-β-gal) staining and immunofluorescence imaging of γH2AX. HDFs were exposed to varying doses of UVA, and CD26 expression levels were analyzed via Western blot. CD26 was subsequently knocked down using lentiviral infection, and signaling pathway proteins related to photoaging, including MAPK/Nrf2 and Smad, were examined.
Results:
In the VISIA skin scoring assessments, the experimental group (IAG) showed significant improvements in spots and red areas after just one treatment (p < 0.001), whereas the IPL group required three treatments to achieve similar results. In the mouse model, both dermal thickness and the Type I collagen content significantly increased following the IAG combination and IPL treatments. Additionally, CD26 expression was significantly elevated in the tissues of the photoaging model, as well as in the post-IPL treatment group. CD26 expression in the photoaging cell model was found to improve and exhibited a dose- and time-dependent relationship with UVA exposure in fibroblasts. After single and repeated UVA exposure, CD26 knockdown led to increased staining of the DNA damage marker γH2AX and the senescence marker β-galactosidase. Furthermore, levels of phosphorylated Smad (p-Smad) and NRF2 decreased after both single and repeated UVA exposures. While p38 and ERK phosphorylation increased after single UVA exposure but decreased following repeated exposure, MMP3 expression was significantly exacerbated by CD26 knockdown in the single-dose model but showed no further significant elevation in the repeated irradiation model.
Conclusions:
Combined IAG therapy achieves a more rapid therapeutic response than IPL monotherapy. Mechanistically, CD26 acts as a potential modulator of photoaging by regulating Smad-mediated collagen synthesis and Nrf2-associated signaling, suggesting CD26 as a potential candidate for further investigation in mitigating skin photo-damage. Notably, the clinical cohort was limited to 20 participants with Fitzpatrick skin Type IV, while this is representative of East Asian populations, the results may not fully extend to other skin types, and larger multi-ethnic studies are warranted.
