Androgen actions in mouse wound healing: Minimal in vivo effects of local antiandrogen delivery
Androgen actions in mouse wound healing: Minimal in vivo effects of local antiandrogen delivery
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雄激素在小鼠伤口愈合中的作用：局部抗雄激素递送的体内影响最小
DOI：
10.1111/wrr.12420
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发表时间：
2016
影响因子：
2.9
通讯作者：
P. Maitz
中科院分区：
文献类型：
--
作者：
Yiwei Wang;U. Simanainen;K. Cheer;F. G. Suarez;Y. Gao;Zhe Li;David Handelsman;P. Maitz
这项工作的目的是确定雄激素在女性伤口愈合中的作用，并开发和表征具有抗雄激素的新型伤口敷料。雄激素延缓男性伤口愈合，但其在女性伤口愈合中的作用尚未确定。为了了解雄激素受体（AR）介导的雄激素在男性和女性伤口愈合中的作用，我们利用了整体AR敲除（ARKO）小鼠模型，突变的AR删除了第二个锌指，以破坏DNA结合和转录激活。AR失活通过增加再上皮化和胶原沉积来提高雄性动物的伤口愈合率，即使在伤口收缩消除时也是如此。与野生型（WT）成纤维细胞相比，ARKO雄性成纤维细胞的细胞增殖和迁移显著增加。然而，ARKO雌性动物的愈合率与WT雌性动物相似。为了利用伤口愈合中的局部抗雄激素作用，同时最大限度地减少脱靶全身效应，我们开发了一种新型电纺聚己内酯（PCL）支架伤口敷料材料，用于持续局部抗雄激素递送。在PCL支架中使用1、5和10 mg/mL的抗雄激素羟基芴醇（HF），在21天内控制HF递送显著增强了人真皮成纤维细胞和人角质形成细胞的体外细胞增殖。与开放性伤口相比，HF-PCL支架也促进了小鼠体内伤口愈合，但与PCL支架相比则不然。
The aims of this work were to define the role of androgens in female wound healing and to develop and characterize a novel wound dressing with antiandrogens. Androgens retard wound healing in males, but their role in female wound healing has not been established. To understand androgen receptor (AR)‐mediated androgen actions in male and female wound healing, we utilized the global AR knockout (ARKO) mouse model, with a mutated AR deleting the second zinc finger to disrupt DNA binding and transcriptional activation. AR inactivation enhanced wound healing rate in males by increasing re‐epithelialization and collagen deposition even when wound contraction was eliminated. Cell proliferation and migration in ARKO male fibroblasts was significantly increased compared with wild‐type (WT) fibroblasts. However, ARKO females showed a similar healing rate compared to WT females. To exploit local antiandrogen effects in wound healing, while minimizing off‐target systemic effects, we developed a novel electrospun polycaprolactone (PCL) scaffold wound dressing material for sustained local antiandrogen delivery. Using the antiandrogen hydroxyl flutamide (HF) at 1, 5, and 10 mg/mL in PCL scaffolds, controlled HF delivery over 21 days significantly enhanced in vitro cell proliferation of human dermal fibroblasts and human keratinocytes. HF‐PCL scaffolds also promoted in vivo wound healing in mice compared with open wounds but not to PCL scaffolds.
DOI：
10.1172/jci16288
发表时间：
2003-05
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
G. Ashcroft;S. Mills;K. Lei;L. Gibbons;M. Jeong;Marisu Taniguchi;M. Burow;M. Horan;S. Wahl;T. Nakayama
通讯作者：
G. Ashcroft;S. Mills;K. Lei;L. Gibbons;M. Jeong;Marisu Taniguchi;M. Burow;M. Horan;S. Wahl;T. Nakayama
5α-还原酶抑制剂非那雄胺和抗雄激素氟他胺对前列腺和生殖器分化的影响比较：剂量反应研究。
影响因子：
4.8
作者：
Imperato-McGinley,J;Sanchez,RS;Spencer,JR;Yee,B;Vaughan,ED
通讯作者：
Vaughan,ED
影响因子：
15.9
作者：
Lai, Jiann-Jyh;Lai, Kuo-Pao;Chang, Chawnshang
通讯作者：
Chang, Chawnshang