FIBROBLAST PROTEOGLYCANS AND CONNECTIVE TISSUE MATRIX

结缔组织是几种大分子的复合体，每种大分子都有自己的 特定的遗传分子特征和生物合成过程。 基质的一种成分中的分子缺陷可能导致缺陷性的 在许多层面上的相互作用，因为特异性结合之间 细胞外分子已经改变，或者因为细胞外分子的反馈调节， 生物合成导致细胞内加工的改变 和其他基质成分的细胞外量。 假设， 在这些实验中测试的是，改变胶原代谢的结果 在蛋白多糖代谢的继发性改变中，产生结构 以及结缔组织复合体的功能变化。 体外 实验已经证明蛋白聚糖的类型和浓度可以 特别影响胶原纤维形成。 正常成人皮肤产生蛋白多糖的数量和类型 外植体和从这些外植体建立的皮肤成纤维细胞系 将被确定，以提供这些基线 调查事务所 数量，类型，定位，标记动力学和 将比较这些正常细胞产生的蛋白聚糖的周转 对来自患者的细胞进行了类似的测定， I型或III型胶原蛋白结构和代谢的缺陷已经被 与胶原蛋白和结缔组织分泌减少有关 疾病（成骨不全和Ehlers-Danlos综合征， 分别）。 通过这些方法产生的不溶性基质的形态 将通过免疫荧光显微镜和免疫荧光显微镜来描述培养中的细胞。 电镜 此外，还将检查蛋白多糖代谢 在正常和受影响个体的真皮外植体培养物中， 确定在培养中注意到的改变是否也在 细胞在其组织环境中。 如果没有发现差异， 这意味着胶原蛋白的生物合成和运输途径， 蛋白聚糖是分开的，产生改变的细胞外比例， 这些大分子可以影响基质结构。 如果 蛋白聚糖代谢在胶原蛋白缺陷的细胞中改变， 将指出这些分子的共调节类型。 增加 了解胶原蛋白和蛋白多糖之间的关系， 调节功能性结缔组织基质的形成将是 有助于理解伴随结缔组织的变化， 更常见的情况，如正常老化。

Connective tissue is a complex of several macromolecules, each with its own specific inherited molecular characteristics and biosynthetic processing. A molecular defect in one component of the matrix could lead to defective interactions at many levals either because specific binding between extracellular molecules has been altered or because feedback regulation of biosynthesis has resulted in alterations of the intracellular processing and extracellular quantity for other matrix components. The hypothesis to be tested in these experiments is that altered collagen metabolism results in secondary alterations in proteoglycan metabolism, producing structural and functional changes in the connective tissue complex. In vitro experiments have demonstrated that proteoglycan type and concentration can specifically influence collagen fibrillogenesis. The quantity and type of proteoglycans produced by normal adult dermal explants and skin fibroblast cell lines established from these explants will be determined, in order to provide the baseline for these investigations. The quantity, type, localization, labeling kinetics and turnover of proteoglycans produced by these normal cells will be compared with similar determinations for cells from patients for whom a specific defect in type I or type III collagen structure and metabolism has been associated with decreased secretion of that collagen and connective tissue disease (osteogenesis imperfecta and Ehlers-Danlos syndrome, respectively). The morphology of the insoluble matrix produced by these cells in culture will be described by immunofluorescence microscopy and by electron microscopy. In addition, proteoglycan metabolism will be examined in dermal explant cultures from normal and affected individuals in order to determine whether the alterations noticed in culture are also found in cells in their tissue environment. If no differences are found it will mean that the biosynthetic and transport pathways for collagen and proteoglycans are separate, producing an altered extracellular ratio for these macromolecules that could influence matrix structure. If proteoglycan metabolism is altered in cells with the collagen defects, some type of co-regulation of these molecules will be indicated. Increased understanding of the relationship between collagen and proteoglycans in regulating the formation of a functional connective tissue matrix will be useful in understanding the alterations of connective tissue that accompany much more common conditions, such as normal aging.