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）分隔表皮和真皮隔室，是提供粘附基底和动态界面两者的高度复杂的结构，从而控制皮肤的整体结构完整性。它作为一种屏障，限制表皮和真皮之间的分子通道，但允许在生理和病理条件下迁移的细胞通过。此外，BM及其组分是细胞活性（例如生长、分化、迁移）的调节剂，并且它们影响组织发育和修复。巢原（nidogen-1和nidogen-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，在小鼠中的NID基因的任一个的缺失仅导致轻微的变化，而没有组织或BM结构的改变，表明家族内的部分冗余。事实上，两种巢蛋白同种型缺陷的小鼠在出生后不久死亡，显示出一系列可直接归因于BM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中巢蛋白的组织特异性功能。尽管巢蛋白双缺失小鼠显示两种巢蛋白的部分冗余，但在巢蛋白-1或-2缺陷小鼠中的伤口愈合研究和肿瘤侵袭实验提供了同种型特异性功能的证据。因此，本项目的主要目标是更深入地了解皮肤生理学和病理学中的同种型特异性功能，并分析这些差异背后的机制。