BASEMENT MEMBRANE ZONE MOLECULAR AND CELL BIOLOGY

基底膜区分子和细胞生物学

• 批准号: 2080432
• 负责人: G SCOTT HERRON
• 金额: $ 97.01万
• 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/2080432
• 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。 以及皮肤不同基底膜区的细胞生物学， 包括表皮-真皮界面和血管基底膜 区域。这个项目的目标集中在描述表情和 重要的基底膜带蛋白的调控 涉及正常生理和生理的病理生理事件 大疱性表皮松解症(EB)。我们将尝试定义结构和 与基底膜带功能完整性有关的蛋白质 并对它们的合成、分泌和调节机制进行表征 退化。 具体项目如下。我。“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基因多态 遗传性EB，并定义获得性EB和 哈哈。二、《角质形成细胞运动和蛋白水解酶表达》将检验 角质形成细胞的黏附和迁移行为 迁移细胞表达的金属蛋白水解酶。三. 《真皮微血管基底膜的代谢》将探讨 正常和活化内皮细胞合成基质蛋白及 将这些细胞的行为与来自 EB患者。四、“细胞外基质的表达调控 正常和RDEB成纤维细胞中的分子和降解酶 “单层培养和重组皮肤模型”是基于 认为过度的蛋白质分解是理解 结缔组织破坏是RDEB的特征。它将探索 金属蛋白酶在三维结构中表达的调控机制 再造皮肤的模型。五.《生物相互作用的生物学》 有基底膜的角质形成细胞“将决定moesin，a 肝素结合受体蛋白，可能在细胞-细胞和 细胞-基质相互作用在细胞铺展、生长和运动中的作用 正常和EB的表皮发育和伤口愈合 派生的细胞。 最终，我们希望这些研究将导致更好地理解 基底膜带的功能和作用更有效 EB的治疗方法。