EXTRACELLULAR COMPARTMENTS--MATRIX DEVELOPMENT & REPAIR

细胞外区室——基质发育

• 批准号: 2079184
• 负责人: DAVID E BIRK
• 金额: $ 19.21万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2079184
• 关键词: chick embryo; chondroitin sulfate B; collagen; connective tissue development; cornea; early embryonic stage; endopeptidases; extracellular matrix; fibroblasts; fibrogenesis; gestational age; histogenesis; immunocytochemistry; immunoelectron microscopy; metalloenzyme; procollagen; proteoglycan; tendons

Collagen assembly into extracellular matrices will be studied during morphogenesis, growth, and repair. Tendon, cornea and dermal fibroblasts establish a hierarchy of extracellular spaces associated with fibrils, bundles, and tissue specific aggregates during development. The distinct domains provide a mechanism for the fibroblast to influence the extracellular steps in matrix assembly. A discontinuous fibrillar matrix is assembled, and fibril segments, about 10 microm long, are deposited into bundles by the 14-day chick embryo tendon fibroblast. We propose that the fibril segment is a normal assembly intermediate, permitting orderly linear, lateral, and intercalary development as well as growth. The size, structure, and fate of fibril segments during different stages of development will be defined using electron microscopy, serial sections, and three dimensional reconstruction techniques. Fibril segments at different stages of development also will be extracted, morphologically characterized, analyzed chemically, and these data correlated with those obtained in situ. In early stages of development, segments are extractable as discrete units while at later stages this may not be the case. We hypothesize that a linear and/or lateral fusion of segments may be responsible for longer, thicker, more mature fibrils. Changes in the fibril surface may mediate these fusions and the ability to chemically analyze segments will permit the identifi- cation of differences related to development or tissue source. The assembly of segments followed by a post- depositional maturation may be an important general mechanism. To test this, fibril segments will be studied during morphogenesis of the chick cornea and dermis, as well as during repair. Constituents of the extracellular compartments will be localized immunochemically. Changes in the surface properties of the segments and/or the interfibrillar matrix may be related to compositional differences in the compartments resulting in the addition or removal of specific proteoglycans, collagen types, propeptides or other macromolecules. Understanding the mechanisms involved in collagen fibril formation, deposition, and the development of connective tissue architecture in situ will contribute to our understanding of development, growth, injury and repair as well as inherited disorders.

胶原蛋白组装成细胞外基质将在 形态发生生长和修复 肌腱、角膜和真皮成纤维细胞 建立与原纤维相关的细胞外空间的层次结构， 束和组织特异性聚集体。 鲜明的 结构域为成纤维细胞提供了一种机制， 细胞外基质组装步骤。 不连续的纤维状基质 组装，并将约10微米长的原纤维片段沉积到 14日龄鸡胚肌腱成纤维细胞成束。 我们建议 原纤维节是正常的组装中间体， 线性、侧向和居间发育以及生长。 尺寸、 结构和命运的原纤维片段在不同阶段的 将使用电子显微镜、连续切片和 三维重建技术。 纤维节段在不同的 发展阶段也将被提取，形态学 特征，化学分析，这些数据与那些 在原地获得。 在发育的早期阶段， 作为离散单元，而在后面的阶段可能不是这种情况。 我们 假设节段线性和/或侧向融合可 形成更长更厚更成熟的纤维 变化 原纤维表面可能介导这些融合， 分析片段将允许识别与 发展或组织来源。 一段接一段， 沉积成熟可能是一个重要的一般机制。 测试 在鸡的形态发生过程中， 角膜和真皮，以及在修复过程中。 成分 细胞外区室将被免疫化学定位。 变化 片段和/或原纤间基质的表面性质可以 与隔室中的成分差异有关， 添加或去除特定的蛋白聚糖，胶原类型， 前肽或其它大分子。 了解相关机制 在胶原纤维的形成、沉积和结缔组织的发育中， 原位组织结构将有助于我们理解 发育、生长、损伤和修复以及遗传性疾病。