Origin of Myofibroblasts in Lung Fibrosis
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LUNG INJURY & FIBROSIS (CL WILSON, SECTION EDITOR)
Origin of Myofibroblasts in Lung Fibrosis CF Hung 1 Accepted: 14 October 2020 # The Author(s) 2020
Abstract Purpose of Review In this brief review, we will highlight important observational and experimental data in the literature that address the origin of scar-forming cells in lung fibrosis. Recent Findings Several cellular sources of activated scar-forming cells (myofibroblasts) have been postulated including alveolar epithelial cells; circulating fibrocytes; and lung stromal cell subpopulations including resident fibroblasts, pericytes, and resident mesenchymal stem cells. Recent advances in lineage-tracing models, however, fail to provide experimental evidence for epithelial and fibrocyte origins of lung myofibroblasts. Resident mesenchymal cells of the lung, which include various cell types including resident fibroblasts, pericytes, and resident mesenchymal stem cells, appear to be important sources of myofibroblasts in murine models of lung injury and fibrosis. Summary Lung myofibroblasts likely originate from multiple sources of lung-resident mesenchymal cells. Their relative contributions may vary depending on the type of injury. Although lineage-tracing experiments have failed to show significant contribution from epithelial cells or fibrocytes, they may play important functional roles in myofibroblast activation through paracrine signaling. Keywords Lung fibrosis . Myofibroblasts . Fibroblasts . Pericytes . Fibrocytes . Epithelial–mesenchymal transition
Introduction Myofibroblasts are activated cells responsible for depositing extracellular matrix (ECM) proteins in scar tissue during fibrogenesis. They exhibit enhanced contractility capable of closing open wounds and tissue repair. Myofibroblasts play an integral role in normal wound healing through (ECM) remodeling, hemostasis, and restoration of tissue barrier integrity. Yet, myofibroblasts are also responsible for pathologies encountered in fibrosing diseases where dysregulated activation of myofibroblasts leads to over-exuberant secretion of ECM proteins and replacement of normal organ architecture, ultimately leading to organ failure. Our limited understanding of where these myofibroblasts originate in disease states and the mechanisms by which myofibroblasts become dysregulated This article is part of the Topical Collection on Lung Injury & Fibrosis * CF Hung [email protected] 1
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Center for Lung Biology, University of Washington, Box 358052, 850 Republican St, Seattle, WA 98109, USA
has been an important barrier to finding effective therapies. This is especially true in the lung, where fibrosing lung diseases such as idiopathic pulmonary fibrosis (IPF) continue to have limited therapeutic options and poor outcomes. Identifying the origin of myofibroblasts is an important step in understanding mechanisms that are responsible for fibrosis as well as to more therapeutic targets in fibrosing diseases.
Defining the Myofibr
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