title: PPARδ inhibits UVB-induced secretion of MMP-1 through MKP-7-mediated suppression of JNK signaling.
abstract: In the present study, we investigated the role of peroxisome proliferator-activated receptor (PPAR) δ in modulating matrix-degrading metalloproteinases and other mechanisms underlying photoaging processes in the skin. In human dermal fibroblasts (HDFs), activation of PPARδ by its specific ligand GW501516 markedly attenuated UVB-induced secretion of matrix metalloproteinase (MMP)-1, concomitant with decreased generation of reactive oxygen species. These effects were significantly reduced in the presence of PPARδ small interfering RNA and GSK0660. Furthermore, c-Jun N-terminal kinase (JNK), but not p38 or extracellular signal-regulated kinase, mediated PPARδ-dependent inhibition of MMP-1 secretion in HDFs exposed to UVB. PPARδ-mediated messenger RNA stabilization of mitogen-activated protein kinase phosphatase (MKP)-7 was responsible for the GW501516-mediated inhibition of JNK signaling. Inhibition of UVB-induced secretion of MMP-1 by PPARδ was associated with the restoration of types I and III collagen to levels approaching those in cells not exposed to UVB. Finally, in HR-1 hairless mice exposed to UVB, administration of GW501516 significantly reduced wrinkle formation and skin thickness, downregulated MMP-1 and JNK phosphorylation, and restored the levels of MKP-7, types I and III collagen. These results suggest that PPARδ-mediated inhibition of MMP-1 secretion prevents some effects of photoaging and maintains the integrity of skin by inhibiting the degradation of the collagenous extracellular matrix.
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors: Sun A
authors: SA
authors: Ham
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors: Eun S
authors: ES
authors: Kang
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors: Hanna
authors: H
authors: Lee
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors: Jung S
authors: JS
authors: Hwang
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors: Taesik
authors: T
authors: Yoo
authors: Department of Nursing, Semyung University, Jechon, Republic of Korea.
authors: Kyung S
authors: KS
authors: Paek
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors: Chankyu
authors: C
authors: Park
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors: Jin-Hoi
authors: JH
authors: Kim
authors: Department of Applied Bioscience, College of Life Science, CHA University, Seongnam, Republic of Korea.
authors: Dae-Seog
authors: DS
authors: Lim
authors: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea. Electronic address: hgseo@konkuk.ac.kr.
authors: Han G
authors: HG
authors: Seo
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D051379:Mice; D008812:Mice, Hairless; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism*; D047494:PPAR delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D061251:Primary Cell Culture; D015595:Skin Aging / Q000473:pathology*; D013844:Thiazoles / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C425931:GW 501516; D047494:PPAR delta; D013844:Thiazoles; D054639:Mitogen-Activated Protein Kinase Phosphatases; C439065:DUSP16 protein, human; D054637:Dual-Specificity Phosphatases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1