Regulation of epidermal barrier wound repair

表皮屏障伤口修复的调节

基本信息

批准号：
7335592
负责人：
WILLIAM JAMES MCGINNIS
金额：
$ 25.05万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
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：
2007-01-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7335592
关键词：
Affect Animals Applications Grants Binding Sites Biochemical Biological Assay Cells Chitin Synthase Cicatrix Code DNA Binding Defect Drosophila genus Embryo Enhancers Environment Epidermis Genes Genetic Genetic Epistasis Genetic Models Genetic Screening Genetic Transcription Genetic screening method Head Healed Health Hereditary Disease Human Injury Insecta Larva Learning Liquid substance Mammals Mediating Molecular Biology Multiple Trauma Mus Mutation Pathway interactions Prevention Receptor Signaling Regulation Regulatory Element Reporter Research Personnel Response Elements Sepsis Signal Pathway Signal Transduction Signal Transduction Pathway Signaling Molecule Site Skin Stratum corneum Structure Testing Transglutaminases Work Wound Healing Wound Repair Pathway Zalcitabine healing improved keratinocyte microbial mutant novel pathogen repaired research study response soft tissue transcription factor transglutaminase 1 wound

Affect Animals Applications Grants Binding Sites Biochemical Biological Assay Cells Chitin Synthase Cicatrix Code DNA Binding Defect Drosophila genus Embryo Enhancers Environment Epidermis Genes Genetic Genetic Epistasis Genetic Models Genetic Screening Genetic Transcription Genetic screening method Head Healed Health Hereditary Disease Human Injury Insecta Larva Learning Liquid substance Mammals Mediating Molecular Biology Multiple Trauma Mus Mutation Pathway interactions Prevention Receptor Signaling Regulation Regulatory Element Reporter Research Personnel Response Elements Sepsis Signal Pathway Signal Transduction Signal Transduction Pathway Signaling Molecule Site Skin Stratum corneum Structure Testing Transglutaminases Work Wound Healing Wound Repair Pathway Zalcitabine healing improved keratinocyte microbial mutant novel pathogen repaired research study response soft tissue transcription factor transglutaminase 1 wound

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项目摘要

We intend to characterize a novel epidermal barrier wound response pathway in Drosophila. The . epidermis of both insects and mammals erects a largely impermeable barrier that preventsdehydration, limits injury to soft tissue, and blocks microbial invasion. A major component of this barrier in insects is the cuticular layer, and a major component in mammals is the stratum corneum of the skin. Recent findings from our lab and others indicate that a conservedgenetic pathway, mediated by Grainy head transcription factors, is used in both insects and mammals to regulate the constructionand repair of the epidermal barrier. Thus, we now have the exciting prospect of applying the strengths of Drosophila genetics and molecular biology to the study of epidermal barrier repair in animals. To identify newgenes and molecules in the barrier wound repair pathway, we will perform genetic screens to identify the signaling molecules and receptorsthat inform epidermal cells of their proximity to barrier woundsites. We will also mutagenize barrier wound responsecis-regulatory elements to determine the DNA binding sites required to activate transcription in responseto aseptic wounds,and the factors that act throughthose binding sites. We will perform assays to identify the intracellular signals and biochemical mechanisms that instruct wound pathway transcription factors to activatewound responseenhancers after aseptic injury. A better understanding of this barrier wound repair pathway should improve human health, as the proposed researchwill identify new genes and molecules that can be tested for their influence on epidermal barrier healing in humans. The importance of the human epidermal barrier is documentedby the scoresof tragic and disfiguring human genetic diseases in which the barrier is compromised, by the need for rapid repair of the barrier in the prevention of sepsis and fluid loss in wounded humans, and by the need for properly regulated barrier replacement in the prevention of scarring.

我们打算表征果蝇中新型的表皮屏障响应途径。这。昆虫和哺乳动物的表皮均建立了不可渗透的障碍，可防止甲基水。限制了软组织的损伤，并阻止微生物侵袭。昆虫中这种障碍的主要组成部分是表皮层和哺乳动物的主要成分是皮肤的角膜。最新发现从我们的实验室和其他实验室中表明，由颗粒状的头部转录介导的保守基因途径因子在昆虫和哺乳动物中都用于调节表皮屏障的修复和修复。因此，我们现在有了激动人心的前景，即应用果蝇遗传学和分子的强度生物学研究动物表皮屏障修复。为了鉴定屏障伤口修复途径中的新基因和分子，我们将执行遗传筛选以识别信号分子和受体，这使表皮细胞接近表皮细胞障碍物。我们还将诱变屏障伤口反应性调节元件以确定激活Respesto无菌伤口中转录所需的DNA结合位点，以及这些因素通过双胞胎结合位点起作用。我们将进行测定以识别细胞内信号和生化指示伤口途径转录因子的机制以激活的响应响应者之后无菌损伤。更好地了解这种障碍伤口修复途径应改善人类健康，因为拟议的研究将确定可以对其对表皮的影响进行测试的新基因和分子人类的障碍愈合。人类表皮屏障的重要性记录在得分由于需要快速而导致障碍所妥协的悲惨和毁容人类遗传疾病。在预防败血症和受伤人类的液体损失方面修复障碍物，并需要在预防疤痕方面，适当调节障碍物。