Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction

作者：Shin Mi Hee; Lee Se Rah; Kim Min Kyoung; Shin Chang Yup; Lee Dong Hun^*; Chung Jin Ho^*

来源：PLos One, 2016, 11(9): e0162628.

DOI：10.1371/journal.pone.0162628

Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a nuclear hormone receptor involved in the transcriptional regulation of lipid metabolism, fatty acid oxidation, and glucose homeostasis. Its activation stimulates antioxidant enzymes such as catalase, whose expression is decreased in aged human skin. Here we investigated the expression of PPAR alpha in aged and ultraviolet (UV)-irradiated skin, and whether PPAR alpha activation can modulate expressions of matrix metalloproteinase (MMP)-1 and procollagen through catalase regulation. We found that PPAR alpha mRNA level was significantly decreased in intrinsically aged and photoaged human skin as well as in UV-irradiated skin. A PPAR alpha activator, Wy14643, inhibited UV-induced increase of MMP-1 and decrease of procollagen expression and caused marked increase in catalase expression. Furthermore, production of reactive oxygen species (ROS) was suppressed by Wy14643 in UV-irradiated and aged dermal fibroblasts, suggesting that the PPAR alpha activation-induced upregulation of catalase leads to scavenging of ROS produced due to UV irradiation or aging. PPAR alpha knockdown decreased catalase expression and abolished the beneficial effects of Wy14643. Topical application of Wy14643 on hairless mice restored catalase activity and prevented MMP-13 and inflammatory responses in skin. Our findings indicate that PPAR alpha activation triggers catalase expression and ROS scavenging, thereby protecting skin from UV-induced damage and intrinsic aging.

• 出版日期2016-9-9