LINKING OPTICS AND MECHANICS IN AIRWAY MODELS OF FIBROSIS

连接纤维化气道模型中的光学和力学

• 批准号: 8169522
• 负责人: Steven CARL George
• 金额: $ 0.21万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169522
• 关键词: Acute; Address; Asthma; Biological; Biological Assay; Breathing; Chemicals; Chronic; Collagen; Computer Retrieval of Information on Scientific Projects Database; Connective Tissue; Cornea; Development; Diagnostic; Diffuse; Disease; Embryonic Development; Epithelial; Epithelium; Fibrosis; Funding; Gel; Grant; Growth; Human; In Vitro; Infection; Inflammatory; Injury; Institution; Interleukin-13; Intubation; Lamina Propria; Laser Scanning Microscopy; Link; Mechanics; Mediator of activation protein; Microscopic; Modeling; Molecular; Mucous Membrane; Obstruction; Optical Coherence Tomography; Optics; Oryctolagus cuniculus; Population; Property; Research; Research Personnel; Resources; Respiratory physiology; Role; Severity of illness; Signal Pathway; Skin; Source; Stress; Structure; Structure of parenchyma of lung; Symptoms; Techniques; Tissue Engineering; Tissue Model; Tissues; Transforming Growth Factors; United States; United States National Institutes of Health; Wound Healing; airway remodeling; bronchial epithelium; in vivo Model; insight; minimally invasive; novel; protein expression; response; wound

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Airway epithelial injury occurs following inhalation of toxic agents, infection, intubation, and in a chronic repetitive disease such as asthma which impacts approximately 10% of the population in the United States. The wound repair response of the epithelium can induce changes in the structure and mechanical properties of the underlying connective tissue that can alter normal lung function. In bronchial asthma, alterations in the airway mucosa become more prominent as the disease progresses, and are correlated with disease severity, symptoms, and lung function (i.e., fixed airflow obstruction). The bronchial epithelium is known to modulate the development of the lung parenchyma during embryogenesis and these signaling pathways are likely "re-awakened" during chronic inflammatory diseases such as asthma resulting in pathological tissue growth. Our central hypothesis is that the wounded and inflamed epithelium secretes soluble mediators which diffuse into the underlying stroma at biologically active concentrations to significantly influence the mechanical properties of the matrix. Our specific aims are structured to specifically address the role of the epithelium in modulating the mechanical and optical properties of the subepithelial matrix: 1) utilizing both physical (compressive and scrape) and chemical (IL-13) injuries to the normal human bronchial epithelium in vitro, characterize the resulting impact on the optical and mechanical properties of the subepithelial matrix; 2) characterize the relationship between optical endpoints and the mechanical properties of both acellular and cellularized collagen gels in which collagen content, microstructure, and transforming growth factor-b2 are systematically altered; 3) quantify changes in the optical and mechanical properties of the tracheal mucosa in a rabbit model of repeated airway epithelial injury. The proposal combines novel tissue engineering techniques which mimic the anatomical arrangement of the epithelium and lamina propria, conventional biological techniques to assess protein expression, non-traditional minimally-invasive optical techniques (multiphoton laser scanning microscopy and optical coherence tomography) to assess bulk and microscopic changes in the matrix, and an in vivo model of tracheal epithelial injury. Completion of these aims will provide insight into the underlying mechanisms of airway remodeling, and provide a platform for non-invasive diagnostics for not only the airway, but other epithelial tissues subject to chronic or acute injury (e.g., cornea, skin). Three aims are addressed in this project: 1) Integrate validated molecular assays of collagen expression with new non-invasive optical techniques, 2) characterize the response of the in vitro tissue model to a physical denudation wound to the epithelium, and 3) characterize the response of the in vitro tissue model to a compressive stress wound to the epithelium.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在吸入有毒药物，感染，插管以及在慢性重复性疾病（例如哮喘）中吸入后，气道上皮损伤发生了，影响了美国约10％的人口。上皮的伤口修复反应可引起可以改变正常肺功能的基础结缔组织的结构和机械性能的变化。在支气管哮喘中，随着疾病的发展，气道粘膜的改变变得更加突出，并且与疾病的严重程度，症状和肺功能相关（即固定的气流阻塞）。 已知支气管上皮在胚胎发生过程中调节肺实质的发育，并且这些信号通路可能在慢性炎性疾病（例如哮喘导致病理组织生长）中“重新唤醒”。 我们的中心假设是，受伤和发炎的上皮分泌可溶性介体，这些介体在生物活性浓度下扩散到基础基质中，以显着影响基质的机械性能。 我们的具体目的旨在特异性地解决上皮下皮下矩阵的机械和光学特性的作用：1）利用物理（压缩和刮擦）以及化学（IL-13）损伤，以及对正常的人支气管上皮的损伤，对体外的人性支气管上皮的影响，表征了副本的特征和机械性能的副标。 2）表征光学终点与细胞和细胞化胶原蛋白凝胶的机械性能之间的关系，其中胶原蛋白，微结构和转化生长因子-B2是系统地改变的； 3）量化气管上皮损伤的兔模型中气管粘膜的光学和机械性能的变化。 The proposal combines novel tissue engineering techniques which mimic the anatomical arrangement of the epithelium and lamina propria, conventional biological techniques to assess protein expression, non-traditional minimally-invasive optical techniques (multiphoton laser scanning microscopy and optical coherence tomography) to assess bulk and microscopic changes in the matrix, and an in vivo model of tracheal上皮损伤。这些目标的完成将提供有关气道重塑的基本机制的洞察力，并为不仅气道，其他受到慢性或急性损伤的上皮组织提供了非侵入性诊断的平台（例如，角膜，皮肤）。 该项目在该项目中解决了三个目的：1）将经过验证的胶原蛋白表达的分子测定与新的非侵入性光学技术相结合，2）表征体外组织模型对上皮的物理剥离的响应，而3）表征体外组织模型对上皮层的体外组织模型的反应。