Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis

Mubarak, Kamal K.; Montes-Worboys, Ana; Regev, Doron; Nasreen, Najmunnisa; Mohammed, Kamal A.; Faruqi, Ibrahim; Hensel, Edward; Baz, Maher A.; Akindipe, Olufemi; Fernández-Bussy, Sebastián; Nathan, Steven D.; Antony, Veena B.

doi:10.1183/09031936.00141010

Cited by 71 publications

(68 citation statements)

References 45 publications

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“…Evidence to support this hypothesis has come largely from analysis of cultured PMCs (13,22) and from analyses of marker gene expression in histological sections of human IPF samples and murine models (22). More recently, studies pointed to migration of postnatal PMC-derived cells into the lung parenchyma in vivo during a 4 hour observation period after TGF-b1 stimulation (3).…”

Section: Discussionmentioning

confidence: 99%

Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis

Gise

Stevens

Honor

et al. 2016

Am J Respir Cell Mol Biol

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The lung is enveloped by a layer of specialized epithelium, the pulmonary mesothelium. In other organs, mesothelial cells undergo epithelialmesenchymal transition and contribute to organ stromal cells. The contribution of pulmonary mesothelial cells (PMCs) to the developing lung has been evaluated with differing conclusions. PMCs have also been indirectly implicated in lung fibrosis in the progressive, fatal lung disease idiopathic pulmonary fibrosis. We used fetal or postnatal genetic pulse labeling of PMCs to assess their fate in murine development, normal lung homeostasis, and models of pulmonary fibrosis. We found that most fetal PMC-derived mesenchymal cells (PMCDCs) expressed markers of pericytes and fibroblasts, only a small minority expressed smooth muscle markers, and none expressed endothelial cell markers. Postnatal PMCs did not contribute to lung mesenchyme during normal lung homeostasis or in models of lung fibrosis. However, fetal PMCDCs were abundant and actively proliferating within fibrotic regions in lung fibrosis models, suggesting that they actively participate in the fibrotic process. These data clarify the role of fetal and postnatal PMCDCs in lung development and disease.

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Section: Discussionmentioning

confidence: 99%

Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis

Gise

Stevens

Honor

et al. 2016

Am J Respir Cell Mol Biol

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“…Pleural mesothelial cells (PMCs) have been implicated in the process of transformation into myofibroblasts and migration, both in vitro [81] and in vivo [82], through a TGF-β1-dependent mechanism called mesothelial-mesenchymal transition. PMCs are present in IPF lungs, and their number correlates with IPF severity [83]. The specific role of PMCs in SSc-ILD needs to be investigated further.…”

Section: Pericytes and Pleural Mesothelial Cells: Underestimated Contmentioning

confidence: 99%

Cellular interactions in the pathogenesis of interstitial lung diseases

2015

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Interstitial lung disease (ILD) encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF) represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells). New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis. @ERSpublications Distinct cell populations contribute to the complex pathogenesis of IPF and systemic sclerosisassociated ILD http://ow.ly/AjFaz

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“…Myofibroblasts are differentiated fibroblasts that express ␣-smooth muscle actin and secrete significantly greater amounts of collagen and ECM components than their fibroblast counterparts (188). The source of fibroblasts that differentiate into myofibroblasts in fibrotic tissue is an area of contention, with studies supporting migration of local fibroblasts into the alveolar space (134), transformation of local epithelial cells into cells expressing mesenchymal markers through epithelial-to-mesenchymal transformation (EMT) (77), transformation of lung pericytes and pleural mesothelial cells into myofibroblasts (120,123), and homing of bone marrow-derived cells of the monocyte lineage (fibrocytes) into areas of injury (134). Since local fibroblasts populations are plentiful in the lung it may seem surprising that other cellular sources are required to produce myofibroblasts.…”

Section: Production Of Excess Collagenmentioning

confidence: 99%

Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis

McKleroy

Lee

Atabai

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

210

169

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Pulmonary fibrosis is a vexing clinical problem with no proven therapeutic options. In the normal lung there is continuous collagen synthesis and collagen degradation, and these two processes are precisely balanced to maintain normal tissue architecture. With lung injury there is an increase in the rate of both collagen production and collagen degradation. The increase in collagen degradation is critical in preventing the formation of permanent scar tissue each time the lung is exposed to injury. In pulmonary fibrosis, collagen degradation does not keep pace with collagen production, resulting in extracellular accumulation of fibrillar collagen. Collagen degradation occurs through both extracellular and intracellular pathways. The extracellular pathway involves cleavage of collagen fibrils by proteolytic enzyme including the metalloproteinases. The less-well-described intracellular pathway involves binding and uptake of collagen fragments by fibroblasts and macrophages for lysosomal degradation. The relationship between these two pathways and their relevance to the development of fibrosis is complex. Fibrosis in the lung, liver, and skin has been associated with an impaired degradative environment. Much of the current scientific effort in fibrosis is focused on understanding the pathways that regulate increased collagen production. However, recent reports suggest an important role for collagen turnover and degradation in regulating the severity of tissue fibrosis. The objective of this review is to evaluate the roles of the extracellular and intracellular collagen degradation pathways in the development of fibrosis and to examine whether pulmonary fibrosis can be viewed as a disease of impaired matrix degradation rather than a disease of increased matrix production.

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Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis

Cited by 71 publications

References 45 publications

Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis

Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis

Cellular interactions in the pathogenesis of interstitial lung diseases

Always cleave up your mess: targeting collagen degradation to treat tissue fibrosis

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