PPARd Inhibits UVB-Induced Secretion of MMP-1 through MKP-7-Mediated Suppression of JNK Signaling

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PPARd Inhibits UVB-Induced Secretion of MMP-1
through MKP-7-Mediated Suppression of JNK Signaling

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PPARd Inhibits UVB-Induced Secretion of MMP-1 through MKP-7-Mediated Suppression of JNK Signaling

  1. 1. Mohamed Antar Aziz Mohamed 2013-11-11
  2. 2. INTRODUCTION  Peroxisome proliferator–activated receptor (PPAR) d is a ligand-inducible transcription factor that modulates multiple biological functions pertaining to skin homeostasis.  PPARδ is abundantly and ubiquitously expressed in a variety of cell lineages, including skin-derived cells, and has been implicated in diverse aspects of skin physiology.  It has also been postulated that PPAR δ is a key mediator of epidermal and dermal aspects of the wound-healing process: it converts extracellular inflammatory signals into organized patterns of gene expression, which eventually leads to the survival, migration, and differentiation of keratinocytes.
  3. 3.  In fact, ligand-activated PPAR δ promotes wound healing by upregulating TGF-β1mediated expression of the extracellular matrix proteins in human keratinocytes and fibroblasts.  On the basis of its beneficial properties, including the acceleration of wound healing and the regulation of inflammatory responses and cellular senescence, PPAR δ is a promising target for the treatment of skin disorders.  In fact, UVB-mediated production of ROS increases MMP secretion in human dermal fibroblasts (HDFs) through MAPK pathway. Therefore, blockade of MMPs may represent one strategy for preventing UV-initiated photodamage caused by a complex cascade of biochemical reactions in the skin. To elucidate the role of PPAR δ in UV-induced cellular damage using HDFs.
  4. 4. RESULTS  PPAR δ inhibits UVB-induced secretion of MMP-1
  5. 5.  PPAR δ suppresses ROS generation induced by UVB radiation
  6. 6.  PPAR δ inhibits the UVB-induced activation of JNK
  7. 7.  MKP-7 is stabilized by PPAR δ
  8. 8.  PPAR δ prevents UVB-induced degradation of collagen I and III
  9. 9.  PPAR δ prevents UVB-induced skin deformity in HR-1 hairless mice
  10. 10. DISCUSSION 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 PPAR δ -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.

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