| First Author | Ham SA | Year | 2013 |
| Journal | J Invest Dermatol | Volume | 133 |
| Issue | 11 | Pages | 2593-2600 |
| PubMed ID | 23639976 | Mgi Jnum | J:202383 |
| Mgi Id | MGI:5518968 | Doi | 10.1038/jid.2013.202 |
| Citation | Ham SA, et al. (2013) PPARdelta Inhibits UVB-Induced Secretion of MMP-1 through MKP-7-Mediated Suppression of JNK Signaling. J Invest Dermatol 133(11):2593-600 |
| abstractText | In the present study, we investigated the role of peroxisome proliferator-activated receptor (PPAR) delta in modulating matrix-degrading metalloproteinases and other mechanisms underlying photoaging processes in the skin. In human dermal fibroblasts (HDFs), activation of PPARdelta 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 PPARdelta small interfering RNA and GSK0660. Furthermore, c-Jun N-terminal kinase (JNK), but not p38 or extracellular signal-regulated kinase, mediated PPARdelta-dependent inhibition of MMP-1 secretion in HDFs exposed to UVB. PPARdelta-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 PPARdelta 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 PPARdelta-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. |
