Estrogen promotes cutaneous wound healing via estrogen receptor β independent of its antiinflammatory activities
Open Access
- 23 August 2010
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 207 (9), 1825-1833
- https://doi.org/10.1084/jem.20100500
Abstract
Post-menopausal women have an increased risk of developing a number of degenerative pathological conditions, linked by the common theme of excessive inflammation. Systemic estrogen replacement (in the form of hormone replacement therapy) is able to accelerate healing of acute cutaneous wounds in elderly females, linked to its potent antiinflammatory activity. However, in contrast to many other age-associated pathologies, the detailed mechanisms through which estrogen modulates skin repair, particularly the cell type-specific role of the two estrogen receptors, ER alpha and ER beta, has yet to be determined. Here, we use pharmacological activation and genetic deletion to investigate the role of both ER alpha and ER beta in cutaneous tissue repair. Unexpectedly, we report that exogenous estrogen replacement to ovariectomised mice in the absence of ER beta actually delayed wound healing. Moreover, healing in epidermal-specific ER beta null mice (K14-cre/ER beta(L2/L2)) largely resembled that in global ER beta null mice. Thus, the beneficial effects of estrogen on skin wound healing are mediated by epidermal ER beta, in marked contrast to most other tissues in the body where ER alpha is predominant. Surprisingly, agonists to both ER alpha and ER beta are potently antiinflammatory during skin repair, indicating clear uncoupling of inflammation and overall efficiency of repair. Thus, estrogen-mediated antiinflammatory activity is not the principal factor in accelerated wound healing.Keywords
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