Tobacco smoke extract induces age-related changes due to modulation of TGF-beta

Exp Dermatol. 2003;12 Suppl 2:51-6. doi: 10.1034/j.1600-0625.12.s2.8.x.

Abstract

We have recently shown that tobacco smoking, like ultraviolet A radiation, is an important factor contributing to premature skin aging. We found that tobacco smoke extract decreased type I and III procollagen, increased tropoelastin mRNA, and induced abnormal accumulation of proteoglycans and matrix metalloproteinase (MMP)-1 and MMP-3 in cultured skin fibroblasts. This indicated that common molecular features might underlie the premature aging of the skin induced by tobacco smoke extract, including abnormal regulation of extracellular matrix deposition through elevated MMPs, reduced collagen production, abnormal tropoelastin accumulation, and altered proteoglycans. With the exception that reactive oxygen species were mediated in the aging process, transforming growth factor (TGF)-beta1 was found to play a crucial role in the age-related alterations induced by tobacco smoke extract. Here we report that tobacco smoke extract blocks cellular responsiveness to TGF-beta1 through the induction of a non-functional latent form of TGF-beta1, and downregulation of the TGF-beta1 receptor. This paper shows the evidence for the role of tobacco smoking in skin aging and describes how modulation of TGF-beta1 levels might retard premature skin aging.

MeSH terms

  • Aging / metabolism*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Matrix Metalloproteinase 1 / genetics
  • Protein-Serine-Threonine Kinases
  • RNA, Messenger / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Skin / metabolism
  • Skin / pathology
  • Smoke / adverse effects*
  • Tobacco*
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / therapeutic use
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2

Substances

  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Smoke
  • TGFB1 protein, human
  • TGFB2 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta2
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Matrix Metalloproteinase 1