Estrogen deficiency and tobacco smoke exposure promote matrix metalloproteinase-13 activation in skin of aging B6 mice

Noor Kassira, Marilyn K. Glassberg, Christina Jones, David J. Pincus, Sharon J. Elliot, Jason R. Fritz, Michael Karl, Seth Thaller

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Estrogen deficiency may contribute to extracellular matrix turnover in skin. This has led previous authors to postulate that aged skin heals less efficiently when compared to younger skin. Also, cigarette smokers have been shown to heal less efficiently than nonsmokers. Matrix metalloproteinase (MMP)-13, an enzyme that participates in the degradation of the extracellular matrix, has been implicated in physiologic aging and wound healing. This study investigates the effects of smoke exposure and estrogen deficiency on MMP-13 in young and aged female mouse skin. Young and aged female C57Bl/6J mice were ovariectomized. They were then randomly administered either 17β-estradiol (E2) or placebo pellets. Half the animals in each age group were further randomized to exposure to cigarette smoke for a period of 6 months. Smoking and estrogen deficiency increased MMP-13 protein and activity in aged skin. The tissue inhibitors of metalloproteinases, which inhibit MMPs, activity was unchanged across all groups. E2 replacement decreased the actual level of MMP-13 protein and activity. We also found an increased collagen content and decreased ER receptor protein level in aged, smoke-exposed female mice. Our experimental data show that tobacco smoke exposure and estrogen deficiency are additive risk factors for promoting increased activity of MMP-13 in aged skin. These findings suggest that MMP-13 functions as a mediator of smoke-induced skin injury in susceptible, aged experimental female mice.

Original languageEnglish (US)
Pages (from-to)318-322
Number of pages5
JournalAnnals of Plastic Surgery
Issue number3
StatePublished - Sep 2009
Externally publishedYes


  • Collagenolysis
  • Estrogen
  • Extracellular matrix
  • Matrix-metalloproteinase 13
  • Smoking

ASJC Scopus subject areas

  • Surgery


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