Basal and UV-induced MMP-1 expression are inhibited by p53 in human dermal fibroblasts

Exp Dermatol. 2008 Nov;17(11):939-45. doi: 10.1111/j.1600-0625.2008.00729.x. Epub 2008 Jun 14.

Abstract

Ultraviolet (UV) triggers induction of matrix metalloproteinase-1 (MMP-1) and also induces the rapid appearance of p53 protein in the epidermis and dermal fibroblasts. However, little is known about the role of p53 on MMP-1 expression in human skin. Here, we investigated the effects of p53 on basal and UV-induced MMP-1 in human dermal fibroblasts. To verify the role of p53 on MMP-1 expression, adenoviral p53 (Ad-p53) gene was infected to human dermal fibroblasts. Our results showed that basal and UV-induced MMP-1 expression was prevented by Ad-p53. In contrast, p53 inhibitor, pifithrin-alpha augmented the UV-induced MMP-1 expression. On the other hand, p53 activator, etoposide, decreased the MMP-1 expression in both normal and p53-overexpressed cells. In addition, MMP-1 expression was not changed by etoposide and/or pifithrin-alpha in HaCaT cells, which have mutation of p53. Taken together, we suggest that p53 inhibits basal and UV-induced MMP-1 expression in human dermal fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Benzothiazoles / pharmacology
  • Blotting, Western
  • Cells, Cultured
  • Dermis / cytology
  • Dermis / metabolism
  • Etoposide / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / radiation effects
  • Humans
  • Matrix Metalloproteinase 1 / metabolism*
  • Phosphorylation / drug effects
  • Phosphorylation / radiation effects
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Toluene / analogs & derivatives
  • Toluene / pharmacology
  • Transduction, Genetic
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology*
  • Ultraviolet Rays*
  • Young Adult

Substances

  • Benzothiazoles
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Tumor Suppressor Protein p53
  • Toluene
  • Etoposide
  • pifithrin
  • Matrix Metalloproteinase 1