BASEMENT MEMBRANE PROTEOGLYCANS

基底膜蛋白聚糖

• 批准号: 3157600
• 负责人: JOHN R. COUCHMAN
• 金额: $ 14.17万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3157600
• 关键词: basement membrane; cell differentiation; cell growth regulation; cell migration; chondroitin sulfates; computer assisted sequence analysis; embryo /fetus cell /tissue; enzyme linked immunosorbent assay; epidermolysis bullosa; extracellular matrix; gene expression; genetic library; heparan sulfate; histochemistry /cytochemistry; human tissue; immunochemistry; immunofluorescence technique; laboratory mouse; laboratory rabbit; laboratory rat; monoclonal antibody; organ culture; protein metabolism; protein sequence; proteoglycan; skin; skin disorder; tissue /cell culture; western blottings

Basement membranes are specialized zones of connective tissue underlying parenchymal cells and separating them from supporting connective tissues. They are composed of a number of macromolecules which interact with each other and with cell surfaces. Functionally they not only provide support and a selective filter but, through cell surface interactions, profoundly influence cell behavior such as growth, migration and differentiation. Heparan sulfate proteoglycan has been identified as an important basement membrane constituent and is implicated in control of basement membrane permeability. We have also identified and partially characterized a basement membrane-specific chondroitin sulfate proteoglycan synthesized by the PYS-2 cell line. Antibodies have been raised against this and the heparan sulfate proteoglycan, purified from bulk cultures, and these stain many mammalian basement membranes. In this proposal we aim to further characterize the proteoglycans and survey their distribution in skin and other basement membranes, with particular emphasis on the embryonic development and ultrastructural studies. The antisera already raised will be exhaustively characterized and monoclonal antibodies will be raised against the PYS-2 chondroitin sulfate proteoglycan. These will assist in immunohistochemical and structural analysis of this newly recognized basement membrane component. The intermolecular interactions between the PYS-2 proteoglycans and other basement membrane macromolecules will also be investigated. It is intended that data concerning the role of basement membrane proteoglycans in the dermal-epidermal junction will be gained which may be of future significance in the study of a wide range of skin diseases where lesions at the basement membrane are an integral part of the pathological process.

基底膜是下面结缔组织的特殊区域 实质细胞并将其与支持结缔组织分离。 它们由许多大分子组成，这些大分子之间相互作用 其他和细胞表面。 从功能上来说，它们不仅提供支持 和选择性过滤器，但通过细胞表面相互作用，深刻地 影响细胞行为，如生长、迁移和分化。 硫酸乙酰肝素蛋白多糖已被确定为重要的基底 膜成分并参与基底膜的控制 渗透性。 我们还确定并部分表征了 基底膜特异性硫酸软骨素蛋白多糖合成 PYS-2细胞系。 已经针对此产生了抗体 硫酸乙酰肝素蛋白多糖，从大量培养物中纯化，这些染色 许多哺乳动物的基底膜。 在本提案中，我们的目标是进一步 表征蛋白多糖并调查其在皮肤中的分布 其他基底膜，特别是胚胎基底膜 发育和超微结构研究。 已经产生的抗血清将 进行详尽的表征并产生单克隆抗体 对抗 PYS-2 硫酸软骨素蛋白多糖。 这些将有助于 对这一新认识的免疫组织化学和结构分析 基底膜成分。 PYS-2蛋白聚糖与其他蛋白之间的分子间相互作用 基底膜大分子也将被研究。 其目的是 有关基底膜蛋白多糖在细胞中的作用的数据 将获得真皮-表皮交界处，这可能是未来的事 在研究多种皮肤病中具有重要意义，其中病变位于 基底膜是病理过程的一个组成部分。