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{"title":"Extracellular Matrix Stiffness in Lung Health and Disease.","authors":"Ting Guo, Chao He, Aida Venado, Yong Zhou","doi":"10.1002/cphy.c210032","DOIUrl":null,"url":null,"abstract":"<p><p>The extracellular matrix (ECM) provides structural support and imparts a wide variety of environmental cues to cells. In the past decade, a growing body of work revealed that the mechanical properties of the ECM, commonly known as matrix stiffness, regulate the fundamental cellular processes of the lung. There is growing appreciation that mechanical interplays between cells and associated ECM are essential to maintain lung homeostasis. Dysregulation of ECM-derived mechanical signaling via altered mechanosensing and mechanotransduction pathways is associated with many common lung diseases. Matrix stiffening is a hallmark of lung fibrosis. The stiffened ECM is not merely a sequelae of lung fibrosis but can actively drive the progression of fibrotic lung disease. In this article, we provide a comprehensive view on the role of matrix stiffness in lung health and disease. We begin by summarizing the effects of matrix stiffness on the function and behavior of various lung cell types and on regulation of biomolecule activity and key physiological processes, including host immune response and cellular metabolism. We discuss the potential mechanisms by which cells probe matrix stiffness and convert mechanical signals to regulate gene expression. We highlight the factors that govern matrix stiffness and outline the role of matrix stiffness in lung development and the pathogenesis of pulmonary fibrosis, pulmonary hypertension, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. We envision targeting of deleterious matrix mechanical cues for treatment of fibrotic lung disease. Advances in technologies for matrix stiffness measurements and design of stiffness-tunable matrix substrates are also explored. © 2022 American Physiological Society. Compr Physiol 12:3523-3558, 2022.</p>","PeriodicalId":10573,"journal":{"name":"Comprehensive Physiology","volume":"12 3","pages":"3523-3558"},"PeriodicalIF":4.2000,"publicationDate":"2022-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088466/pdf/nihms-1883485.pdf","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comprehensive Physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cphy.c210032","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
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Abstract
The extracellular matrix (ECM) provides structural support and imparts a wide variety of environmental cues to cells. In the past decade, a growing body of work revealed that the mechanical properties of the ECM, commonly known as matrix stiffness, regulate the fundamental cellular processes of the lung. There is growing appreciation that mechanical interplays between cells and associated ECM are essential to maintain lung homeostasis. Dysregulation of ECM-derived mechanical signaling via altered mechanosensing and mechanotransduction pathways is associated with many common lung diseases. Matrix stiffening is a hallmark of lung fibrosis. The stiffened ECM is not merely a sequelae of lung fibrosis but can actively drive the progression of fibrotic lung disease. In this article, we provide a comprehensive view on the role of matrix stiffness in lung health and disease. We begin by summarizing the effects of matrix stiffness on the function and behavior of various lung cell types and on regulation of biomolecule activity and key physiological processes, including host immune response and cellular metabolism. We discuss the potential mechanisms by which cells probe matrix stiffness and convert mechanical signals to regulate gene expression. We highlight the factors that govern matrix stiffness and outline the role of matrix stiffness in lung development and the pathogenesis of pulmonary fibrosis, pulmonary hypertension, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. We envision targeting of deleterious matrix mechanical cues for treatment of fibrotic lung disease. Advances in technologies for matrix stiffness measurements and design of stiffness-tunable matrix substrates are also explored. © 2022 American Physiological Society. Compr Physiol 12:3523-3558, 2022.
肺健康和疾病中的细胞外基质僵硬。
细胞外基质(ECM)为细胞提供结构支持和各种环境信号。在过去的十年中,越来越多的研究表明,ECM的力学特性,通常被称为基质刚度,调节肺的基本细胞过程。越来越多的人认识到细胞和相关ECM之间的机械相互作用对于维持肺稳态至关重要。通过机械传感和机械转导途径改变的ecm衍生的机械信号失调与许多常见的肺部疾病有关。基质硬化是肺纤维化的标志。硬化的ECM不仅是肺纤维化的后遗症,而且可以积极地推动纤维化肺病的进展。在这篇文章中,我们提供了一个全面的观点,在肺健康和疾病基质硬度的作用。我们首先总结了基质硬度对各种肺细胞类型的功能和行为的影响,以及对生物分子活性和关键生理过程的调节,包括宿主免疫反应和细胞代谢。我们讨论了细胞通过探测基质刚度和转换机械信号来调节基因表达的潜在机制。我们强调了控制基质刚度的因素,并概述了基质刚度在肺发育和肺纤维化、肺动脉高压、哮喘、慢性阻塞性肺疾病(COPD)和肺癌的发病机制中的作用。我们设想针对有害基质机械线索治疗纤维化肺疾病。还探讨了矩阵刚度测量和刚度可调矩阵基板设计技术的进展。©2022美国生理学会。中国生物医学工程学报(英文版),2012。
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