Department of Physiology and Biophysics, University of Illinois Chicago, Chicago, IL, USA.
University of Illinois Cancer Center, Chicago, IL, USA.
Nat Rev Mol Cell Biol. 2024 Nov;25(11):865-885. doi: 10.1038/s41580-024-00767-3. Epub 2024 Sep 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.
细胞外基质（ECM）是一种复杂的蛋白质和聚糖网格，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发挥着关键作用，从为组织和器官赋予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理解 ECM 在健康和疾病中的功能至关重要。本文综述讨论了基质成分组成多样性的新见解，以及导致组织特异性组装和架构的机制，这些组装和架构旨在支持特定的功能。然后，本文重点介绍了最近发现的机制，包括翻译后修饰和代谢途径，如氨基酸可用性和昼夜节律，这些机制调节 ECM 在稳态和人类疾病中的分泌、组装和重塑。最后，本文探讨了“基质疗法”的潜力，即通过正常化 ECM 组成和结构来实现治疗益处的策略。
