Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction.
Peroxisome proliferator-activated receptor alpha (PPARα) 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 PPARα in aged and ultraviolet (UV)-irradiated skin, and whether PPARα activation can modulate expressions of matrix metalloproteinase (MMP)-1 and procollagen through catalase regulation. We found that PPARα mRNA level was significantly decreased in intrinsically aged and photoaged human skin as well as in UV-irradiated skin. A PPARα 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 PPARα activation-induced upregulation of catalase leads to scavenging of ROS produced due to UV irradiation or aging. PPARα 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 PPARα activation triggers catalase expression and ROS scavenging, thereby protecting skin from UV-induced damage and intrinsic aging.
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.|Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Mi Hee
MH
Shin
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.|Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Se-Rah
SR
Lee
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.|Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Min-Kyoung
MK
Kim
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.|Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Chang-Yup
CY
Shin
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.|Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
Dong Hun
DH
Lee
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.|Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea.|Institute on Aging, Seoul National University, Seoul, Republic of Korea.
Jin Ho
JH
Chung
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000528:radiation effects; D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000201:enzymology* / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D055815:Young Adult
D047493:PPAR alpha; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; D002374:Catalase