Project #2: Elucidating the Effects of Arsenic and Estrogen on Wound Healing

项目总结 皮肤伤口愈合是一个复杂的过程，涉及几个生理和分子方面的因素 受损皮肤组织周围的变化。阻碍伤口的环境污染物 治愈会使个人面临感染和痛苦的风险。类固醇激素和雌激素 特别是对参与伤口愈合的细胞和组织过程产生积极影响，导致 皮肤结构和生理的变化以及创面速度和能力的增加 关闭并愈合，但干扰雌激素信号的污染物可能会阻碍愈合。 无机砷是一种干扰雌激素信号的环境污染物。 流程。虽然有几种可能的途径使人类接触到砷，但在许多地方 世界上最大的水资源提供了重要的接触途径。这种风险对许多原住民来说是真实的 美国人生活在部落社区，那里难以获得含砷的饮用水 存在符合当前美国环保局标准的水平。高砷对健康的影响 暴露是有很好的记录的，但最近的研究发现，即使是中等水平的砷 暴露，如在一些西南部美洲原住民社区中发现的，是 与与健康相关的负面结果有关。这种风险敞口有很大一部分并没有通过 原住民土地上目前的水处理工艺。考虑到美洲原住民在 糖尿病的风险特别高，因此，糖尿病相关伤口是否 激素疗法可以改善伤口结果有可能提供翻译 对这一脆弱人群和其他遭受砷伤害的人都有用的结果 全球受污染地区。这项提议的首要假设是 与环境相关的砷水平将抑制伤口愈合过程以及 类固醇信号传递过程。此外，外源性雌二醇会逆转 砷暴露的影响。目的1测定砷在体外的全剂量效应。 皮肤伤口愈合模型，Aim 2确定雌激素暴露是否逆转 使用相同的体外模型研究砷暴露的影响，目标3不仅决定了 伤口愈合的体内模型验证了体外AIMS的结果，但也 确定临床前模型中的雌激素治疗是否支持局部用药 对食物和水资源中暴露于砷的个人的伤口进行激素治疗。 好了！

PROJECT SUMMARY Cutaneous wound healing is a complex process that involves several physiological and molecular changes surrounding the damaged skin tissue. Environmental contaminants that impede wound healing place individuals at risk for infection and suffering. Steroid hormones, and estrogen in particular, positively influence cellular and tissue processes involved in wound healing, leading to changes in skin structure and physiology and increased shifts in the rate and capacity for wounds to close and heal, but contaminants that interfere with estrogen signaling may impede healing. Inorganic arsenic is an environmental contaminant that interferes with estrogen signaling processes. While there are several potential routes for human exposure to arsenic, in many parts of the world water resources provide a significant exposure route. This risk is real for many Native Americans living in tribal communities where challenges to accessing drinking water with arsenic levels meeting current USEPA standards exist. Health effects resulting from high arsenic exposure are well documented, but recent studies find that even moderate levels of arsenic exposure, such as those identified in some Southwestern Native American communities, are associated with negative health-related outcomes. Much of this exposure is not removed through current water treatment processes on Native lands. Given that Native Americans are at particularly high risk of diabetes and, therefore, diabetes-related wounds determining whether hormonal therapies can improve wound outcomes has the potential to provide translational outcomes useful both to this vulnerable population, and to others experiencing wounds in arsenic contaminated regions globally. The overarching hypothesis of this proposal is that environmentally relevant levels of arsenic will act to inhibit wound healing processes as well as steroid signaling processes. Furthermore, exogenous administration of estradiol will reverse the effects of arsenic exposure. Aim 1 determines the full dose response of arsenic on an in vitro model for cutaneous wound healing, Aim 2 determines whether estrogen exposure reverses the effects of arsenic exposure using the same in vitro model, and Aim 3 determines not only whether an in vivo model of wound healing validates the results found in the in vitro aims, but also determines whether estrogen treatment in a pre-clinical model supports the use of topical hormone therapy on wounds for individuals exposed to arsenic in their food and water resources. !