Minority Predoctoral Fellowship Program

少数族裔博士前奖学金计划

基本信息

批准号：
7618860
负责人：
YOANNIS IMBERT-FERNANDEZ
金额：
$ 2.63万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-01 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7618860
关键词：
Androgen Receptor Androgens Anti-Inflammatory Agents Anti-inflammatory Breast Cancer Cell Cell Communication Cell Line Cell Survival Cell physiology Cells Chronic Complex Country Defense Mechanisms Disease Dry Eye Syndromes Epithelial Epithelial Cells Estrogen Receptor alpha Estrogen Receptors Etiology Excessive tearing Eye diseases Fellowship Program Female Figs - dietary Film Gender Genetic Transcription Goals Growth Homeostasis Human Inflammation Keratoconjunctivitis Sicca Laboratories Lacrimal gland structure MCF7 cell Maintenance Mediating Minority Molecular Mucin-1 Staining Method Mucins Pathogenesis Persons Play Population Postmenopause Production Property Proteins RNA Splicing Role Signal Transduction Stress System Testing Thinking Tissues Variant Woman aqueous biological adaptation to stress evaporation eye dryness hormone regulation novel ocular surface pre-doctoral protective effect

项目摘要

DESCRIPTION (provided by applicant): Dry eye disease is due to tear deficiency or excessive tear evaporation and results in inflammation and damage to the ocular surface. Mucins are highly O-glycosylated proteins that lubricate and protect the ocular surface. Recent findings indicate that the mucin MUC1 has anti-inflammatory properties and also can interact with estrogen receptor-alpha thereby modulating gene transcription. Androgens are key to maintaining homeostasis of the ocular surface. A potential interaction between MUC1 and androgen receptor (AR) could confer additional protection: My long term goal is to elucidate the molecular mechanisms involved in the pathogenesis of dry eye. My hypothesis is that MUC1 and androgen receptor (AR) are key factors that can act together to protect the ocular surface. The hypothesis will be tested by three specific aims: Aim 1- Determine the interaction between MUC1 and AR in human ocular surface epithelial cell lines; Aim 2- Elucidate the anti-inflammatory role of MUC1 and AR in those cells; and Aim 3- We have found that persons expressing the MUC1/A splice variant rather than MUC1/B are less susceptible to dry eye. We will determine if MUC1/A and MUC1/B splice variants differ in their signal transduction capabilities.

描述（由申请人提供）：干眼症是由于撕裂缺乏或泪水蒸发过多，导致炎症和对眼表面的损害。粘蛋白是高度O-糖基化的蛋白，可润滑并保护眼表面。最近的发现表明，粘蛋白MUC1具有抗炎特性，也可以与雌激素受体-Alpha相互作用，从而调节基因转录。雄激素是维持眼表面体内平衡的关键。 MUC1与雄激素受体（AR）之间的潜在相互作用可以提供额外的保护：我的长期目标是阐明干眼症发病机理所涉及的分子机制。我的假设是MUC1和雄激素受体（AR）是可以共同作用以保护眼表面的关键因素。该假设将通过三个特定目的来检验：目标1-确定人眼表面上皮细胞系中MUC1和AR之间的相互作用；瞄准2-阐明MUC1和AR在这些细胞中的抗炎作用； AIM 3-我们发现表达MUC1/A剪接变体而不是MUC1/B的人不太容易受到干眼的影响。我们将确定MUC1/A和MUC1/B剪接变体的信号转导功能是否有所不同。