Comprehensive Pneumology Center, University Hospital of the Ludwig-Maximilians-University Munich and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany
Comprehensive Pneumology Center, University Hospital of the Ludwig-Maximilians-University Munich and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
Eur Respir J. 2017 Jul 5;50(1). doi: 10.1183/13993003.01805-2016. Print 2017 Jul.
The pulmonary extracellular matrix (ECM) determines the tissue architecture of the lung, and provides mechanical stability and elastic recoil, which are essential for physiological lung function. Biochemical and biomechanical signals initiated by the ECM direct cellular function and differentiation, and thus play a decisive role in lung development, tissue remodelling processes and maintenance of adult homeostasis. Recent proteomic studies have demonstrated that at least 150 different ECM proteins, glycosaminoglycans and modifying enzymes are expressed in the lung, and these assemble into intricate composite biomaterials. These highly insoluble assemblies of interacting ECM proteins and their glycan modifications can act as a solid phase-binding interface for hundreds of secreted proteins, which creates an information-rich signalling template for cell function and differentiation. Dynamic changes within the ECM that occur upon injury or with ageing are associated with several chronic lung diseases. In this review, we summarise the available data about the structure and function of the pulmonary ECM, and highlight changes that occur in idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma and lung cancer. We discuss potential mechanisms of ECM remodelling and modification, which we believe are relevant for future diagnosis and treatment of chronic lung disease.
肺细胞外基质（ECM）决定了肺组织的结构，并提供了生理肺功能所必需的机械稳定性和弹性回弹。ECM 引发的生化和生物力学信号指导细胞功能和分化，因此在肺发育、组织重塑过程和维持成人内稳态方面起着决定性作用。最近的蛋白质组学研究表明，肺中至少表达 150 种不同的 ECM 蛋白、糖胺聚糖和修饰酶，这些蛋白组装成复杂的复合生物材料。这些相互作用的 ECM 蛋白及其聚糖修饰的高度不溶性组装可以作为数百种分泌蛋白的固相结合界面，为细胞功能和分化创造了一个信息丰富的信号模板。损伤或衰老时 ECM 内发生的动态变化与几种慢性肺部疾病有关。在这篇综述中，我们总结了有关肺 ECM 的结构和功能的现有数据，并强调了特发性肺纤维化（IPF）、肺动脉高压（PAH）、慢性阻塞性肺疾病（COPD）、哮喘和肺癌中发生的变化。我们讨论了 ECM 重塑和修饰的潜在机制，我们认为这些机制与未来慢性肺部疾病的诊断和治疗有关。
