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      Chronic lung diseases: entangled in extracellular matrix

      review-article
      1 , 2 , 3 , , 1 , 2 , 3
      European Respiratory Review
      European Respiratory Society

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          Abstract

          The extracellular matrix (ECM) is the scaffold that provides structure and support to all organs, including the lung; however, it is also much more than this. The ECM provides biochemical and biomechanical cues to cells that reside or transit through this micro-environment, instructing their responses. The ECM structure and composition changes in chronic lung diseases; how such changes impact disease pathogenesis is not as well understood. Cells bind to the ECM through surface receptors, of which the integrin family is one of the most widely recognised. The signals that cells receive from the ECM regulate their attachment, proliferation, differentiation, inflammatory secretory profile and survival. There is extensive evidence documenting changes in the composition and amount of ECM in diseased lung tissues. However, changes in the topographical arrangement, organisation of the structural fibres and stiffness (or viscoelasticity) of the matrix in which cells are embedded have an undervalued but strong impact on cell phenotype. The ECM in diseased lungs also changes in physical and biomechanical ways that drive cellular responses. The characteristics of these environments alter cell behaviour and potentially orchestrate perpetuation of lung diseases. Future therapies should target ECM remodelling as much as the underlying culprit cells.

          Abstract

          Important biochemical and biomechanical cues from the extracellular matrix are disrupted in chronic lung diseases, altering the fate of resident lung cells and trafficking immune cells, and thereby contributing to disease development and progression https://bit.ly/3FgiQvc

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          Most cited references99

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          Matrix elasticity directs stem cell lineage specification.

          Microenvironments appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. During the initial week in culture, reprogramming of these lineages is possible with addition of soluble induction factors, but after several weeks in culture, the cells commit to the lineage specified by matrix elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types. Inhibition of nonmuscle myosin II blocks all elasticity-directed lineage specification-without strongly perturbing many other aspects of cell function and shape. The results have significant implications for understanding physical effects of the in vivo microenvironment and also for therapeutic uses of stem cells.
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            The extracellular matrix at a glance.

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              Tissue cells feel and respond to the stiffness of their substrate.

              Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.
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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                31 March 2022
                09 March 2022
                : 31
                : 163
                : 210202
                Affiliations
                [1 ]University of Groningen, University Medical Center Groningen, Dept of Pathology and Medical Biology, Groningen, The Netherlands
                [2 ]University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands
                [3 ]University of Groningen, University Medical Center Groningen, KOLFF Institute – REGENERATE, Groningen, The Netherlands
                Author notes
                Corresponding author: Janette Burgess ( j.k.burgess@ 123456umcg.nl )
                Author information
                https://orcid.org/0000-0001-9868-9966
                Article
                ERR-0202-2021
                10.1183/16000617.0202-2021
                9488575
                35264410
                1cb7d992-1a6f-4886-837f-20f7765987fb
                Copyright ©The authors 2022

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org

                History
                : 31 August 2021
                : 17 December 2021
                Categories
                Lung Science Conference Reviews
                12

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