Maintenance and Repair of the C. elegans Skin

秀丽隐杆线虫皮肤的保养和修复

• 批准号: 10531551
• 负责人: Andrew D Chisholm
• 金额: $ 39.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-05 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531551
• 关键词: Address; Adult; Animals; Apical; Basement membrane; Biogenesis; Biology; Body Fluids; Caenorhabditis elegans; Communication; Environment; Epidermis; Epithelium; Extracellular Matrix; Future; Genes; Genetic; Goals; Health; Human; Hypertrophic Cicatrix; Keloid; Knowledge; Life; Lipids; Maintenance; Modeling; Molecular; Nematoda; Opportunistic Infections; Organism; Pathology; Permeability; Research; Role; Site; Skin; Skin repair; Skin wound healing; System; Tissues; Work; acute stress; chronic wound; diabetic ulcer; injury and repair; insight; loss of function; programs; repaired; skin fibrosis; skin organogenesis; skin wound; wound; wound healing

Summary The skin is the primary interface between animals and their external environment. The skin maintains its structural integrity throughout the life of an organism while providing passive and active defenses against external challenges. While understanding of skin development has advanced rapidly in recent years, less is known of how the mature skin is maintained in adult life, including how it heals wounds. More broadly, the mechanisms that maintain mature tissues are still relatively poorly understood. The overall goal of this research program is to understand at the molecular level how a simple skin layer is repaired and maintained during adult life. The system of choice is the skin of the nematode C. elegans, a relatively simple and experimentally tractable model for skin layers. The C. elegans skin comprises a simple epidermal epithelium and associated basal and apical extracellular matrices, the basement membrane and the cuticle. Previous studies have how the mature skin responds to injury and repairs itself. This work led to the discovery of genetic regulators of adult skin maintenance; loss of function in such genes does not affect skin development but results in progressive adult-onset degeneration of the adult skin. Future studies will extend these approaches to dissect how the mature epidermis is maintained in normal and perturbed conditions. The epidermis and extracellular matrices of the skin function as an integrated unit in biogenesis, maintenance and repair. The proposed work will also investigate how the epidermis and extracellular matrix communicate in tissue maintenance and wound repair. These studies will also address the roles of an extracellular matrix lipid layer in formation and repair of the skin permeability barrier. The resulting insights should advance knowledge of skin biology relevant to several aspects of human health, including normal wound healing, chronic wounds, and skin fibrosis in hypertrophic scarring.

概括 皮肤是动物及其外部的主要界面 环境。皮肤在整个生物的生命中保持其结构完整性 同时为外部挑战提供被动和积极的防御能力。尽管 近年来，对皮肤发育的理解迅速发展，知之甚少 关于成人生活如何保持成熟的皮肤，包括如何治愈伤口。更多的 广泛地，维持成熟组织的机制仍然相对较差 理解。该研究计划的总体目标是在分子上了解 平整成人生活中如何修复和维护简单的皮肤层。系统 选择是线虫C.秀丽隐杆线虫的皮肤，这是一种相对简单且实验性的 皮肤层的可拖动模型。秀丽隐杆线虫的皮肤包括一个简单的表皮 上皮以及相关的基础和顶端细胞外矩阵，地下室 膜和角质层。先前的研究具有成熟的皮肤如何应对损伤 并修理自己。这项工作导致发现了成人皮肤的遗传调节剂 维护;这种基因的功能损失不会影响皮肤发育，但结果 在成人皮肤的渐进性成人变性中。未来的研究将扩展 这些方法是为如何保持成熟的表皮如何保持正常和 干扰条件。皮肤的表皮和细胞外矩阵起作用 生物发生，维护和修复中的综合单位。拟议的工作也将 研究表皮和细胞外基质如何​​在组织中通信 维护和伤口修复。这些研究还将解决 细胞外基质脂质层形成和修复皮肤渗透性屏障。这 最终的见解应提高与多个方面相关的皮肤生物学知识 人类健康，包括正常伤口愈合，慢性伤口和皮肤纤维化 肥厚的疤痕。