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J Invest Dermatol. 2013 Nov;133(11):2593-2600. doi: 10.1038/jid.2013.202. Epub 2013 May 2.

PPARδ inhibits UVB-induced secretion of MMP-1 through MKP-7-mediated suppression of JNK signaling.

Author information

1
Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
2
Department of Nursing, Semyung University, Jechon, Republic of Korea.
3
Department of Applied Bioscience, College of Life Science, CHA University, Seongnam, Republic of Korea.
4
Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea. Electronic address: hgseo@konkuk.ac.kr.

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.

PMID:
23639976
DOI:
10.1038/jid.2013.202
[Indexed for MEDLINE]
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