BASEMENT MEMBRANE ZONE MOLECULAR AND CELL BIOLOGY IN EB

EB 中的基底膜区分子和细胞生物学

• 批准号: 3092458
• 负责人: EUGENE A BAUER
• 金额: $ 111.58万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3092458
• 关键词: basement membrane; cellular pathology; epidermolysis bullosa; molecular pathology

The proposed program project will study various aspects of the molecular and cellular biology of various basement membrane zones of the skin, including the epidermal-dermal interface and the vascular basement membrane zone. The goals of this project focus on characterizing expression and regulation of basement membrane zone proteins of importance in pathophysiologic events involved in both normal physiology and epidermolysis bullosa (EB). We shall attempt to define structures and proteins involved in the functional integrity of the basement membrane zone and to characterize mechanisms governing their synthesis, secretion and degradation. The specific projects are as follows. I. "Candidate Protein Clones in EB" will develop and use probes to map genes and establish polymorphisms in hereditary EB and define possible relationships between acquired EB and HLA. II. "Keratinocyte Locomotion and Protease Expression" will examine the attachment and migratory behavior of keratinocytes and characterize the repertoire of metalloproteases expressed by the migrating cells. III. "Metabolism of the Dermal Microvascular Basement Membrane" will examine matrix protein synthesis by normal and activated endothelial cells and compare the behavior of these cells with that of endothelial cells from patients with EB. IV. "Regulation of Expression of Extracellular Matrix Molecules and Degradative Enzymes in Normal and RDEB Fibroblasts in Monolayer Culture and in a Reconstituted Skin Model" is predicated on the notion that excessive proteolysis is fundamental to understanding the connective tissue destruction that characterizes RDEB. It will explore the mechanisms of regulation of metalloprotease expression in a 3-dimensional model of reconstituted skin. V. "Biology of the Interaction of Keratinocytes with Basement Membranes" will determine what role moesin, a heparin-binding receptor protein, may play in processes of cell-cell and cell-matrix interactions in cell spreading, growth and motility of the epidermis during development and wound healing in both normal and EB- derived cells. Ultimately, we hope that these studies will lead to better understanding of the function of the basement membrane zone and to more effective therapeutic approaches to EB.

拟议的计划项目将研究分子的各个方面， 以及皮肤的各种基底膜区域的细胞生物学， 包括表皮-真皮界面和血管基底膜 区 该项目的目标集中在表征表达和 调节基底膜区蛋白的重要性 病理生理事件涉及正常生理和 大疱性表皮炎（EB）。 我们将尝试定义结构， 参与基底膜区功能完整性的蛋白质 并描述其合成、分泌和 降解 具体项目如下。 I.“EB中的候选蛋白质克隆” 将开发和使用探针来绘制基因图谱，并建立多态性， 遗传性EB和定义获得性EB和 HLA 二.“角质细胞运动和蛋白酶表达”将研究 角质形成细胞的附着和迁移行为，并表征 由迁移细胞表达的金属蛋白酶库。 三. “真皮微血管基底膜的代谢”将研究 正常和活化内皮细胞的基质蛋白合成， 比较这些细胞的行为与内皮细胞， EB患者 四.“细胞外基质表达的调节 正常和RDEB成纤维细胞中的分子和降解酶 单层培养和在重建皮肤模型中”是基于 过度的蛋白质水解是理解 结缔组织破坏是RDEB的特征。 将探索 金属蛋白酶表达的三维调控机制 再造皮肤的模型 五、“生物学的相互作用 具有基底膜的角质形成细胞”将决定膜突蛋白的作用， 肝素结合受体蛋白，可能在细胞-细胞过程中起作用， 细胞-基质的相互作用在细胞的扩散，生长和运动的 表皮发育和创伤愈合过程中的正常和EB- 衍生细胞 最终，我们希望这些研究将有助于更好地了解 基底膜区的功能，并更有效地 EB的治疗方法