Age-Associated Increase in Skin Fibroblast-Derived Prostaglandin E2Contributes to Reduced Collagen Levels in Elderly Human Skin

Yong Li, Dan Lei, William R. Swindell, Wei Xia, Shinuo Weng, Jianping Fu, Christal A. Worthen, Toru Okubo, Andrew Johnston, Johann E. Gudjonsson, John J. Voorhees, Gary J. Fisher

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Production of type I collagen declines during aging, leading to skin thinning and impaired function. Prostaglandin E2(PGE2) is a pleiotropic lipid mediator that is synthesized from arachidonic acid by the sequential actions of cyclooxygenases (COX) and PGE synthases (PTGES). PGE2inhibits collagen production by fibroblasts in vitro. We report that PTGES1 and COX2 progressively increase with aging in sun-protected human skin. PTGES1 and COX2 mRNA were increased 3.4-fold and 2.7-fold, respectively, in the dermis of elderly (>80 years) versus young (21-30 years) individuals. Fibroblasts were the major cell source of both enzymes. PGE2levels were increased 70% in elderly skin. Fibroblasts in aged skin display reduced spreading due to collagen fibril fragmentation. To investigate the relationship between spreading and PGE2synthesis, fibroblasts were cultured on micropost arrays or hydrogels of varying mechanical compliance. Reduced spreading/mechanical force resulted in increased expression of both PTGES1 and COX2 and elevated levels of PGE 2. Inhibition of PGE2synthesis by diclofenac enhanced collagen production in skin organ cultures. These data suggest that reduced spreading/mechanical force of fibroblasts in aged skin elevates PGE2production, contributing to reduced collagen production. Inhibition of PGE2production may be therapeutically beneficial for combating age-Associated collagen deficit in human skin.

Original languageEnglish (US)
Pages (from-to)2181-2188
Number of pages8
JournalJournal of Investigative Dermatology
Volume135
Issue number9
DOIs
StatePublished - Sep 18 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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