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Article
Nature Medicine  3, 1209 - 1215 (1997)
doi:10.1038/nm1197-1209

Estrogen accelerates cutaneous wound healing associated with an increase in TGF-bold beta1 levels

Gillian S. Ashcroft1, 2, Joanne Dodsworth1, Egon Van Boxtel2, Roy W. Tarnuzzer3, Michael A. Horan2, Gregory S. Schultz3 & Mark W.J. Ferguson1, 4

  1Cells, Immunology and Development Division, School of Biological Sciences, 3.239 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK

  2Department of Geriatric Medicine, University Hospital of South Manchester, Withington, Manchester M202LR, UK

  3Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida 32610, USA

  4Correspondence should be addressed to M.W.J.F.

The cellular and molecular mechanisms underlying the effects of aging on human cutaneous wound healing are poorly understood, and the possible role of reproductive hormones in this process has never been investigated. We report that aging in healthy females was associated with a reduced rate of cutaneous wound healing, but an improved quality of scarring both microscopically and macroscopically, and with reduced levels of transforming growth factor-beta1 (TGF-beta1) immuno staining and steady-state mRNA in the wound. These age-related changes were reversed by the systemic administration of hormone replacement therapy (HRT). Moreover, ovariectomized young female rodents exhibited a marked delay in repair of acute incisional wounds, which was reversed by the topical application of estrogen. The cellular mechanism underlying these changes appears to involve an estrogen-induced increase in latent TGF-beta1 secretion by dermal fibroblasts. These results suggest that both the rate and quality of wound healing depend on reproductive hormone levels.

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