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Molecular generators at corneal wounds produce and regulate the wound electrical signals

角膜伤口处的分子发生器产生并调节伤口电信号

基本信息

批准号：
9039611
负责人：
Min Zhao
金额：
$ 39.21万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9039611
关键词：
Animals Calcium Cells Chloride Channels Chronic Clinical Confocal Microscopy Cornea Corneal Injury Cues Defect Electric Stimulation Electrophysiology (science)Epithelial Epithelial Cells Family Generations Genetic Models Goals Grant Healed Health Immunofluorescence Immunologic In Vitro Injury Insurance Ion Channel Ion Pumps Ion-Selective Electrodes Ions Keratopathy Knock-out Knockout Mice Knowledge Lead Measures Mechanics Molecular Molecular Biology Molecular Target Physiological Pilot Projects Regulation Resistance Role Side Signal Transduction Site Skin Techniques Technology Testing Western Blotting Wound Healing base chronic wound clinical efficacy corneal epithelium diabetic diabetic patient diabetic rat effective therapy electric field healing improved in vivo insight member migration novel novel strategies patch clamp research study response response to injury therapy development wound

项目摘要

DESCRIPTION (provided by applicant): Our goal is to electrically heal wounds. Experiments from our own lab and others have demonstrated that electric fields occur naturally at corneal wounds and provide a powerful signal to guide migration of corneal epithelial cells. We demonstrated that the electrical signals could override other directional cues, such as injury stimulation, free edge and mechanical forces, in guiding migration of corneal epithelial sheets and large groups of cells. It is however not known how cornea wounds generate the electric "signal". We propose to discover molecular "generators" at corneal wounds. Uncovering these generator molecules will give us molecular targets which we can stimulate to produce stronger electrical signals, and thus facilitate healing. In this proposal, we will 1) characterize calcium-activated chloride channels (CaCCs) in corneal epithelial cells using electrophysiology and genetic models; 2) determine responses of CaCCs to injury and their roles in generating wound electric currents; and, 3) correct the defective wound electric signals (and wound healing) in diabetic rats and ANO1 knockout mice. We expect that the novel mechanisms discovered will provide fundamental insights as well as practical strategies for healing of chronic corneal wounds.

描述（由申请人提供）：我们的目标是用电来治愈伤口。我们自己的实验室和其他实验室的实验表明，电场在角膜伤口处自然发生，并提供强大的信号来引导角膜上皮细胞的迁移。我们证明，电信号可以超越其他方向线索，例如损伤刺激、自由边缘和机械力，引导角膜上皮片和大群细胞的迁移。然而，目前尚不清楚角膜伤口如何产生电“信号”。我们建议在角膜伤口处发现分子“发生器”。发现这些发生器分子将为我们提供分子靶点，我们可以刺激它们产生更强的电信号，从而促进愈合。在本提案中，我们将1）利用电生理学和遗传模型来表征角膜上皮细胞中的钙激活氯离子通道（CaCC）； 2) 确定 CaCC 对损伤的反应及其在产生伤口电流中的作用； 3) 纠正糖尿病大鼠和 ANO1 敲除小鼠中有缺陷的伤口电信号（和伤口愈合）。我们期望所发现的新机制将为慢性角膜伤口的愈合提供基本见解和实用策略。