权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

项目

基本信息

批准号：
9449732
负责人：
Robert Shawn Kellar
金额：
$ 22.23万
依托单位：
NORTHERN ARIZONA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9449732
关键词：
Apoptosis Arsenic Biological Assay Cell Cycle Regulation Cell physiology Cells Collaborations Communities Complex Cutaneous DNA Repair Data Diabetes Mellitus Dose Elderly woman Endocrinology Environmental Exposure Environmental Pollution Environmental Risk Factor Estradiol Estrogens Exposure to Food Gene Expression Genes Geology Health Hispanics In Vitro Individual Infection Inflammation Interdisciplinary Study Knowledge Modeling Molecular Monitor Moon Native Americans Outcome Oxidative Stress Pathway interactions Physiological Physiology Polymerase Chain Reaction Population Populations at Risk Pre-Clinical Model Process Public Health Research Resources Risk Role Route Signal Transduction Skin Skin Tissue Steroids Structure Students Support System Testing Therapeutic Thick Tissues Translational Research Vulnerable Populations Water Work Wound Healing diabetes risk drinking water environmental stressor environmental toxicology experience exposed human population exposure route graduate student healing health disparity health equity high risk hormone therapy improved improved outcome in vitro Model in vivo in vivo Model innovation meetings proteotoxicity response steroid hormone translational medicine tribal community undergraduate student water treatment wound wound closure

项目摘要

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. !

项目总结