Systemic responses to tissue damage and regeneration

对组织损伤和再生的系统反应

• 批准号: 8339079
• 负责人: MEGUMI M. FUSE
• 金额: $ 13.89万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8339079
• 关键词: Ablation; Address; Adult; Agonist; Animal Model; Animals; Area; Biological Assay; Biological Metamorphosis; Biological Models; Blood; Body Size; Cells; Chronic; Collaborations; Coupled; Crustacea; Cystic Fibrosis; Data; Development; Developmental Biology; Developmental Delay Disorders; Digit structure; Disease; Drosophila genus; Drosophila melanogaster; Ecdysteroids; Endocrine; Endocrine system; Endocrinology; Environment; Enzyme-Linked Immunosorbent Assay; Epithelial; Flow Cytometry; Genetic; Genetic Techniques; Goals; Growth; Hemocytes; Hemolymph; High Pressure Liquid Chromatography; Hormones; Human; Immune; Immune system; Immunology; Inflammation; Inflammatory; Injection of therapeutic agent; Injury; Insecta; Insulin; Invertebrates; Laboratories; Larva; Learning; Manduca; Manduca sexta; Marines; Measures; Mentors; Mentorship; Modeling; Molecular Biology; Molecular Genetics; Monitor; Natural regeneration; Operative Surgical Procedures; Organ; Peripheral; Phenotype; Pilot Projects; Population; Primordium; Process; Puberty; Publications; Pupa; Research; Retinoids; Role; Sampling; Signal Transduction; Stress; Structure; Technical Expertise; Techniques; Time; Tissues; Universities; Wing; Wood material; cancer therapy; environmental stressor; imaginal disc; immunocytochemistry; in utero; interest; irradiation; meetings; regenerative; release factor; repaired; response; tissue regeneration; tissue repair

DESCRIPTION (provided by applicant): The current goals of this research are to characterize the systemic responses to tissue regeneration after injury in insects, such as delays in developmental that provide time for the repair of select tissues. Many tissues display an impressive ability for repair and regeneration after injury. This is seen in invertebrate and vertebrate tissues and even in digit replacement in humans in utero. Compensatory growth and regeneration are vital processes used to replace damaged tissue during animal development. Responses to tissue injury and regeneration include inflammation or reduced growth in neighboring cells, as well as changes in growth rate including delays in development. Much is known of the local responses to tissue damage, but there is a gap in information on how local signals produce systemic immune and developmental responses. Insect imaginal discs, the precursors to adult structures such as wings, show exceptional regenerative capabilities, where they secrete signals that delay development when damaged. This project will (i) the characterize responses of the immune system after damage to the imaginal discs, (ii) identify and characterize the factors released from the damaged discs providing signals to the endocrine system, and (ii) determine the actions of these blood-borne factors on the endocrine system. This research will be conducted on the larger insect, Manduca sexta, as a means of developing a complementary model organism to the genetically tractable, but smaller fruitfly, Drosophila melanogaster. Given the mentorship by Dr. Hariharan of UC Berkeley, this pilot project will broaden the scope of the PI's expertise in immunology and development for understanding how development is modulated in response to external stresses, and how tissues interact to monitor changes in growth and body size during development. It will also provide the learning environment for introducing Drosophila genetics to the lab when necessary. PUBLIC HEALTH RELEVANCE: This research broadens our understanding of local responses to tissue repair, looking at the systemic effects of tissue injury. A number of inflammatory diseases such as Cystic Fibrosis or Crohn's display changes in growth and puberty onset, while insulin insensitivity is a result of chronic inflammation. Understanding how signals from damaged tissue interact with the immune system and peripheral endocrine tissues to alter development are key to addressing these problems. Finally, this research may also help understand the damage induced by x-rays during cancer treatments.

描述（由申请人提供）：本研究的当前目标是表征昆虫受伤后组织再生的系统性反应，例如发育延迟，为修复精选组织的修复时间。许多组织在受伤后表现出令人印象深刻的修复和再生能力。这在无脊椎动物和脊椎动物组织中，甚至在子宫内人类的数字替代中都可以看出。补偿性生长和再生是用于替代动物发育过程中受损组织的重要过程。对组织损伤和再生的反应包括炎症或邻近细胞的生长降低，以及增长率的变化，包括发育延迟。众所周知，众所周知，局部对组织损伤的反应，但是有关局部信号如何产生系统性免疫和发育反应的信息存在差距。昆虫想象的圆盘是成年结构（例如机翼）的前体，显示出非凡的再生能力，它们分泌信号，这些信号会延迟损坏时发育。该项目将（i）损坏对想象盘的损坏后免疫系统的响应的特征，（ii）识别并表征从损坏的椎间盘上释放的因素，从而向内分泌系统提供信号，并且（ii）确定这些血液的作用 - 内分泌系统的生长因素。这项研究将以较大的昆虫甘达·塞克斯塔（Manduca Sexta）进行，作为将互补模型的生物开发到可基因拖运但较小的果蝇果蝇果蝇的一种手段。鉴于加州大学伯克利分校的Hariharan博士的指导，该试点项目将扩大PI在免疫学和发展方面的专业知识的范围，以了解如何根据外部压力调节发展，以及组织如何相互作用以监测生长和身体大小的变化在开发过程中。它还将在必要时提供学习环境，以将果蝇遗传学引入实验室。 公共卫生相关性：这项研究扩大了我们对组织损伤的全身影响的当地反应的理解。许多炎症性疾病，例如囊性纤维化或克罗恩（Crohn）的生长和青春期发作的变化，而胰岛素不敏感性是慢性炎症的结果。了解受损组织中的信号如何与免疫系统和周围内分泌组织相互作用以改变发育是解决这些问题的关键。最后，这项研究还可能有助于了解癌症治疗过程中X射线造成的损害。