Role of the basement membrane proteins nidogen-1 and -2 in skin physiology and pathology

基底膜蛋白 nidogen-1 和 -2 在皮肤生理学和病理学中的作用

• 批准号: 46383320
• 负责人: Privatdozentin Dr. Roswitha Nischt (†)
• 金额: --
• 依托单位: Klinik für Dermatologie und Venerologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/46383320?language=en
• 关键词: Role; basement; membrane; proteins; nidogen

The cutaneous basement membrane (BM), which separates the epidermal and dermal compartments, is a highly complex structure providing both an adhesive substrate and a dynamic interface, thus governing the overall structural integrity of the skin. It acts as a barrier that restricts the passage of molecules between epidermis and dermis, but permits the passage of migrating cells under physiological and pathological conditions. Further, BMs and their components are regulators of cellular activities, such as growth, differentiation, migration, and they influence tissue development and repair. The nidogens, nidogen-1 and -2, are related, ubiquitous BM proteins which have been considered to play a key role in BM assembly and stabilization. However, deletion of either of the NID genes in the mouse results in only mild changes with no alteration of tissue or BM architecture indicating partial redundancy within the family. Indeed, mice deficient for both nidogen isoforms die shortly after birth showing a range of abnormalities which could be directly assigned to BM defects. Surprisingly, in some organs ultrastructurally normal BM were found indicating tissue specific functions for nidogens in BMs. Although the nidogen double null mice show partial redundancy for the two nidogens wound healing studies and tumor invasion experiments in either nidogen-1 or -2 deficient mice provide evidence for isoform specific functions. Therefore the main goal of this project will be to gain more insight into the isoform specific functions in skin physiology and pathology and to analyse the mechanisms underlying these differences.

皮肤基底膜 (BM) 分隔表皮和真皮区室，是一种高度复杂的结构，提供粘合基底和动态界面，从而控制皮肤的整体结构完整性。它作为屏障限制表皮和真皮之间的分子通过，但在生理和病理条件下允许迁移细胞通过。此外，BM 及其成分是细胞活动的调节剂，例如生长、分化、迁移，并且它们影响组织发育和修复。 nidogens、nidogen-1 和 -2 是相关的、普遍存在的 BM 蛋白，被认为在 BM 组装和稳定中发挥关键作用。然而，删除小鼠中的任何一个 NID 基因只会导致轻微的变化，而组织或骨髓结构没有改变，表明该家族内部存在部分冗余。事实上，缺乏两种巢蛋白异构体的小鼠在出生后不久就会死亡，表现出一系列可直接归因于骨髓缺陷的异常。令人惊讶的是，在一些器官中发现超微结构正常的 BM，表明 BM 中巢蛋白具有组织特异性功能。尽管 nidogen 双无效小鼠显示出两种 nidogen 伤口愈合研究和肿瘤侵袭实验在 nidogen-1 或 -2 缺陷小鼠中的部分冗余，为亚型特异性功能提供了证据。因此，该项目的主要目标是更深入地了解同种型在皮肤生理学和病理学中的特定功能，并分析这些差异背后的机制。