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: 10064142
• 负责人: Andrew D Chisholm
• 金额: $ 39.43万
• 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/10064142
• 关键词: Address; Adult; Animals; Apical; Basement membrane; Biogenesis; Biology; Caenorhabditis elegans; Environment; Epidermis; Epithelial; Extracellular Matrix; Future; Genes; Genetic; Goals; Health; Human; Hypertrophic Cicatrix; Keloid; Knowledge; Life; Lipids; Liquid substance; Maintenance; Modeling; Molecular; Nematoda; Opportunistic Infections; Organism; Pathology; Permeability; Research; Role; Site; Skin; Skin repair; Skin wound healing; Structure; 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.

总结 皮肤是动物与其外部环境之间的主要界面。 环境皮肤在生物体的整个生命过程中保持其结构的完整性 同时针对外部挑战提供被动和主动防御。而 近年来，对皮肤发育的理解进展迅速，但所知较少。 成熟的皮肤在成年后是如何保持的，包括它如何愈合伤口。更 大体上，维持成熟组织的机制仍然相对较差， 明白这项研究计划的总体目标是在分子水平上了解 水平如何一个简单的皮肤层是修复和维持在成年生活。制度 选择是线虫C的皮肤。一种相对简单， 皮肤层的易处理模型。梭秀丽线虫的皮肤包括一个简单的表皮 上皮和相关的基底和顶端细胞外基质，基底 膜和角质层。以前的研究已经知道了成熟的皮肤对损伤的反应 自我修复这项工作导致了成人皮肤遗传调节因子的发现 维护;这些基因功能的丧失不会影响皮肤发育，但会导致 成人皮肤的进行性退化。未来的研究将扩大 这些方法来剖析成熟表皮是如何保持正常的， 扰动条件。皮肤的表皮和细胞外基质作为一种细胞外基质， 在生物发生、维护和修理方面的综合单元。拟议的工作还将 研究表皮和细胞外基质如何在组织中沟通 维护和伤口修复。这些研究还将探讨 细胞外基质脂质层在皮肤通透性屏障的形成和修复中起重要作用。的 由此产生的见解应该会推进与几个方面相关的皮肤生物学知识 包括正常伤口愈合、慢性伤口和皮肤纤维化， 增生性疤痕