Role and Potential Mechanisms of Peroxisome Proliferator-Activated Receptor α in Ultraviolet B Radiation-Induced Skin Damage

Objective Ultraviolet B radiation (UVB) in sunlight is classified by the WHO as a Group 1 carcinogen. UVB is readily absorbed by the epidermis, and excessive exposure causes skin injury and photoaging. Peroxisome proliferator-activated receptor α (PPARα), a key member of the nuclear receptor family, plays a central role in lipid metabolism. This study aims to observe and investigate the effects of PPARα deletion on the progression of UVB-induced damage and changes in the skin lipid profile using PPARα-knockout (PPARα^－/－) and wild-type mice.

Methods A mouse model of ultraviolet-induced skin damage was established using excessive UVB exposure (2 J/cm²) administered for a single time. C57BL/6J mice were divided into PPARα^－/－ and wild-type groups. Qualitative and quantitative analyses were performed using skin photodamage scoring, hematoxylin-eosin (HE) staining, and Western blotting. A photoaging model was established using repeated low-dose UVB exposure, and the C57BL/6 mice were again divided into PPARα^－/－ and wild-type groups for qualitative and quantitative analyses through HE staining and Western blotting. Skin samples collected from PPARα^－/－ and wild-type mice either sham-irradiated or exposed to a single dose 2 J/cm² UVB irradiation were subjected to lipidomic analysis.

Results In the photodamage model, PPARα^－/－ mice exhibited significantly higher skin photodamage scores and delayed wound healing than wild-type controls on days 0-32 after a single excessive UVB exposure. In the photoaging model, the expression levels of senescence-associated proteins were markedly up-regulated in the skin of PPARα^－/－ mice compared with wide-type mice (wild-type vs. PPARα^－/－) (p16: 0.11 ± 0.02 vs. 0.82 ± 0.18, P < 0.05; p21: 0.54 ± 0.03 vs. 1.29 ± 0.07, P < 0.01; p53: 0.54 ± 0.04 vs. 1.33 ± 0.06, P < 0.01; β-galactosidase: 0.80 ± 0.06 vs. 1.20 ± 0.15, P < 0.05). In addition, PPARα^－/－ mice exhibited reduced numbers of hair follicles and follicular atrophy. Lipidomic analysis revealed that PPARα deletion aggravated UVB-induced skin lipid metabolic disturbances, involving aberrant expression of multiple lipids, including Cer(d18:1/30:2), OAHFA(44:4), PE(50:1), LPC(19:1), LPS(44:11), and PC(19:1/20:1).

Conclusion PPARα plays a protective role in UVB-induced skin damage and photoaging. Its deficiency aggravates skin damage and lipid metabolic disturbances.