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J Invest Dermatol. 2015 Sep;135(9):2181-2188. doi: 10.1038/jid.2015.157. Epub 2015 Apr 23.

Age-Associated Increase in Skin Fibroblast-Derived Prostaglandin E2 Contributes to Reduced Collagen Levels in Elderly Human Skin.

Author information

1
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
2
Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
3
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA. Electronic address: gjfisher@med.umich.edu.

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). PGE2 inhibits 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. PGE2 levels 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 PGE2 synthesis, 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 PGE2. Inhibition of PGE2 synthesis by diclofenac enhanced collagen production in skin organ cultures. These data suggest that reduced spreading/mechanical force of fibroblasts in aged skin elevates PGE2 production, contributing to reduced collagen production. Inhibition of PGE2 production may be therapeutically beneficial for combating age-associated collagen deficit in human skin.

PMID:
25905589
PMCID:
PMC4537382
DOI:
10.1038/jid.2015.157
[Indexed for MEDLINE]
Free PMC Article

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