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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen Type I / metabolism
  • Collagen Type III / metabolism
  • Dermis / cytology
  • Dermis / metabolism
  • Dermis / radiation effects
  • Dual-Specificity Phosphatases / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • MAP Kinase Signaling System / radiation effects
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 13 / metabolism*
  • Mice
  • Mice, Hairless
  • Mitogen-Activated Protein Kinase Phosphatases / metabolism*
  • PPAR delta / antagonists & inhibitors
  • PPAR delta / metabolism*
  • Primary Cell Culture
  • Skin Aging / pathology*
  • Thiazoles / pharmacology
  • Ultraviolet Rays / adverse effects


  • Collagen Type I
  • Collagen Type III
  • GW 501516
  • PPAR delta
  • Thiazoles
  • Mitogen-Activated Protein Kinase Phosphatases
  • DUSP16 protein, human
  • Dual-Specificity Phosphatases
  • Matrix Metalloproteinase 13
  • Mmp13 protein, mouse
  • MMP1 protein, human
  • Matrix Metalloproteinase 1