Estrogen promotes cutaneous wound healing via estrogen receptor beta independent of its antiinflammatory activities.
Estrogen promotes cutaneous wound healing via estrogen receptor beta independent of its antiinflammatory activities.
复制标题
DOI：
10.1084/jem.20100500
复制
发表时间：
2010-08-30
期刊：
影响因子：
--
通讯作者：
Hardman MJ
中科院分区：
文献类型：
--
作者：
Campbell L;Emmerson E;Davies F;Gilliver SC;Krust A;Chambon P;Ashcroft GS;Hardman MJ
绝经后妇女患上许多退行性病理学疾病的风险增加，这些疾病与过度炎症的共同主题有关。全身性雌激素替代疗法（以激素替代疗法的形式）能够加速老年女性急性皮肤伤口的愈合，这与其有效的抗氧化活性有关。然而，与许多其他年龄相关的病理学相反，雌激素调节皮肤修复的详细机制，特别是两种雌激素受体ERα和ERβ的细胞类型特异性作用，尚未确定。在这里，我们使用药理学激活和基因缺失来研究ERα和ERβ在皮肤组织修复中的作用。出乎意料的是，我们报告说，在缺乏ERβ的情况下，对卵巢切除小鼠进行外源性雌激素替代实际上延迟了伤口愈合。此外，表皮特异性ERβ缺失小鼠（K14-cre/ERβL2/L2）的愈合情况与整体ERβ缺失小鼠的愈合情况非常相似。因此，雌激素对皮肤伤口愈合的有益作用是由表皮ERβ介导的，与ERα占主导地位的体内大多数其他组织形成鲜明对比。令人惊讶的是，ERα和ERβ的激动剂在皮肤修复过程中是有效的，表明炎症的明显解偶联和修复的总体效率。因此，雌激素介导的促炎活性不是加速伤口愈合的主要因素。
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, ERα and ERβ, has yet to be determined. Here, we use pharmacological activation and genetic deletion to investigate the role of both ERα and ERβ in cutaneous tissue repair. Unexpectedly, we report that exogenous estrogen replacement to ovariectomised mice in the absence of ERβ actually delayed wound healing. Moreover, healing in epidermal-specific ERβ null mice (K14-cre/ERβL2/L2) largely resembled that in global ERβ null mice. Thus, the beneficial effects of estrogen on skin wound healing are mediated by epidermal ERβ, in marked contrast to most other tissues in the body where ERα is predominant. Surprisingly, agonists to both ERα and ERβ 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.