Burgess Janette K, Gosens Reinoud
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, the Netherlands; Department of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands.
Biochem Pharmacol. 2024 Oct;228:116255. doi: 10.1016/j.bcp.2024.116255. Epub 2024 May 3.
The lung is a biomechanically active organ, with multiscale mechanical forces impacting the organ, tissue and cellular responses within this microenvironment. In chronic lung diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and others, the structure of the lung is drastically altered impeding gas exchange. These changes are, in part, reflected in alterations in the composition, amount and organization of the extracellular matrix within the different lung compartments. The transmission of mechanical forces within lung tissue are broadcast by this complex mix of extracellular matrix components, in particular the collagens, elastin and proteoglycans and the crosslinking of these components. At both a macro and a micro level, the mechanical properties of the microenvironment have a key regulatory role in ascertaining cellular responses and the function of the lung. Cells adhere to, and receive signals from, the extracellular matrix through a number of different surface receptors and complexes which are important for mechanotransduction. This review summarizes the multiscale mechanics in the lung and how the mechanical environment changes in lung disease and aging. We then examine the role of mechanotransduction in driving cell signaling events in lung diseases and finish with a future perspective of the need to consider how such forces may impact pharmacological responsiveness in lung diseases.
肺是一个具有生物力学活性的器官，多尺度机械力影响着该微环境中的器官、组织和细胞反应。在慢性肺部疾病中，如慢性阻塞性肺疾病、肺纤维化等，肺的结构会发生剧烈改变，从而阻碍气体交换。这些变化部分反映在不同肺腔室中细胞外基质的组成、数量和组织的改变上。肺组织内机械力的传递是由细胞外基质成分的这种复杂混合物介导的，特别是胶原蛋白、弹性蛋白和蛋白聚糖以及这些成分的交联。在宏观和微观层面，微环境的机械特性在确定细胞反应和肺功能方面都起着关键的调节作用。细胞通过许多不同的表面受体和复合物与细胞外基质粘附并接收信号，这些受体和复合物对机械转导很重要。本综述总结了肺中的多尺度力学以及机械环境在肺部疾病和衰老过程中的变化。然后，我们研究了机械转导在驱动肺部疾病细胞信号事件中的作用，并展望了未来需要考虑这些力如何影响肺部疾病的药理反应性。
