Nature Reviews Molecular Cell Biology ( IF 81.3 ) Pub Date : 2024-09-02 , DOI: 10.1038/s41580-024-00767-3 Alexandra Naba 1, 2
The extracellular matrix (ECM) is the complex meshwork of proteins and glycans that forms the scaffold that surrounds and supports cells. It exerts key roles in all aspects of metazoan physiology, from conferring physical and mechanical properties on tissues and organs to modulating cellular processes such as proliferation, differentiation and migration. Understanding the mechanisms that orchestrate the assembly of the ECM scaffold is thus crucial to understand ECM functions in health and disease. This Review discusses novel insights into the compositional diversity of matrisome components and the mechanisms that lead to tissue-specific assemblies and architectures tailored to support specific functions. The Review then highlights recently discovered mechanisms, including post-translational modifications and metabolic pathways such as amino acid availability and the circadian clock, that modulate ECM secretion, assembly and remodelling in homeostasis and human diseases. Last, the Review explores the potential of ‘matritherapies’, that is, strategies to normalize ECM composition and architecture to achieve a therapeutic benefit.
中文翻译:
细胞外基质的组装和重塑机制
细胞外基质 (ECM) 是蛋白质和聚糖的复杂网状结构,形成围绕和支持细胞的支架。它在后生动物生理学的各个方面都发挥着关键作用,从赋予组织和器官的物理和机械特性到调节细胞过程,如增殖、分化和迁移。因此,了解协调 ECM 支架组装的机制对于了解 ECM 在健康和疾病中的功能至关重要。本综述讨论了对基质体成分组成多样性的新见解,以及导致为支持特定功能而定制的组织特异性组装和结构的机制。然后,该综述强调了最近发现的机制,包括翻译后修饰和代谢途径,例如氨基酸可用性和生物钟,这些机制调节体内平衡和人类疾病中 ECM 的分泌、组装和重塑。最后,本综述探讨了“基质疗法”的潜力,即使 ECM 组成和结构正常化以实现治疗益处的策略。