Extracellular matrix composition in COPD

Annoni, Raquel; Lanças, Tatiana; Tanigawa, Ryan; Matsushita, Marcus de Medeiros; Fernezlian, Sandra; Bruno, Andreina; Silva, Luiz Fernando Ferraz da; Roughley, Peter J.; Battaglia, Salvatore; Dolhnikoff, Marisa; Hiemstra, Pieter S.; Sterk, Peter J.; Rabe, Klaus F.; Mauad, Thaís

doi:10.1183/09031936.00192611

Cited by 114 publications

(139 citation statements)

References 45 publications

(50 reference statements)

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“…These data suggest that glycoproteins, released from fibroblasts, may play an important role in TGF-b1-mediated myofibroblast differentiation, resulting in a feed-forward loop. Increased peribronchial deposition of collagen, a-SMA, TNC, and FN in patients with emphysema suggests a similar mechanism of aberrant repair after epithelial injury, with resultant airway remodeling and airflow obstruction in COPD (79,80). However, our current understanding of the role of specific glycoproteins in the matrix remodeling associated with emphysema is limited.…”

Section: Elastinmentioning

confidence: 95%

“…The antifibrotic effects of decorin have been attributed to inhibition of TGF-b1 activity through binding of the patent peptide to leucine-rich repeats in the core protein (92,93). There is no difference in peribronchial or parenchymal deposition of decorin in mild/moderate COPD compared with normal lungs; however, decreased expression of peribronchiolar decorin has been shown in patients with severe emphysema (79,94). In addition, TGF-b1 has been shown to down-regulate decorin expression in fibroblasts from patients with severe emphysema compared with fibroblasts from patients with mild emphysema (95).…”

Section: Proteoglycansmentioning

confidence: 99%

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Matrix Remodeling in Pulmonary Fibrosis and Emphysema

Kulkarni

O’Reilly

Antony

et al. 2016

Am J Respir Cell Mol Biol

107

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Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-b1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema.

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Section: Elastinmentioning

confidence: 95%

Section: Proteoglycansmentioning

confidence: 99%

Matrix Remodeling in Pulmonary Fibrosis and Emphysema

Kulkarni

O’Reilly

Antony

et al. 2016

Am J Respir Cell Mol Biol

107

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“…In disease, these rates likely vary, although data are sparse in humans. Pathologic fragmentation and degradation of ECM also contribute to tissue stiffness; recent data suggest damage to elastin fibers with increased fractional area of fibronectin and tenascin in chronic obstructive pulmonary disease (COPD) airways, which will alter stiffness of the ECM (27). Similarly, robust collagen deposition in fibrotic disorders such as idiopathic pulmonary fibrosis (IPF) is associated with marked increases in lung stiffness (4).…”

Section: Modulation Of Ecm Stiffnessmentioning

confidence: 99%

Lung Extracellular Matrix and Fibroblast Function

2015

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Extracellular matrix (ECM) is a tissue-specific macromolecular structure that provides physical support to tissues and is essential for normal organ function. In the lung, ECM plays an active role in shaping cell behavior both in health and disease by virtue of the contextual clues it imparts to cells. Qualities including dimensionality, molecular composition, and intrinsic stiffness all promote normal function of the lung ECM. Alterations in composition and/or modulation of stiffness of the focally injured or diseased lung ECM microenvironment plays a part in reparative processes performed by fibroblasts. Under conditions of remodeling or in disease states, inhomogeneous stiffening (or softening) of the pathologic ECM may both precede modifications in cell behavior and be a result of disease progression. The ability of ECM to stimulate further ECM production by fibroblasts and drive disease progression has potentially significant implications for mesenchymal stromal cell-based therapies; in the setting of pathologic ECM stiffness or composition, the therapeutic intent of progenitor cells may be subverted. Taken together, current data suggest that lung ECM actively contributes to health and disease; thus, mediators of cell-ECM signaling or factors that influence ECM stiffness may represent viable therapeutic targets in many lung disorders.

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“…They are increased in respiratory diseases such as asthma and COPD, and their presence is associated with structural remodeling and/or inflammation in the airways (5,38). However, the reasons why they accumulate remain unclear.…”

mentioning

confidence: 99%

Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts

Burgess

Brock

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts. Am J Physiol Lung Cell Mol Physiol 303: L239-L250, 2012. First published May 25, 2012 doi:10.1152/ajplung.00097.2012.-Eicosanoids are lipid-signaling mediators released by many cells in response to various stimuli. Increasing evidence suggests that eicosanoids such as leukotrienes and prostaglandins (PGs) may directly mediate remodeling. In this study, we assessed whether these substances could alter extracellular matrix (ECM) proteins and the inflammatory profiles of primary human airway smooth muscle cells (ASM) and fibroblasts. PGE 2 decreased both fibronectin and tenascin C in fibroblasts but only fibronectin in ASM. PGD 2 decreased both fibronectin and tenascin C in both ASM and fibroblasts, whereas PGF 2␣ had no effect on ECM deposition. The selective PGI2 analog, MRE-269, decreased fibronectin but not tenascin C in both cell types. All the PGs increased IL-6 and IL-8 release in a dose-dependent manner in ASM and fibroblasts. Changes in ECM deposition and cytokine release induced by prostaglandins in both ASM and fibroblasts were independent of an effect on cell number. Neither the acute nor repeated stimulation with leukotrienes had an effect on the deposition of ECM proteins or cytokine release from ASM or fibroblasts. We concluded that, collectively, these results provide evidence that PGs may contribute to ECM remodeling to a greater extent than leukotrienes in airway cells.

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Extracellular matrix composition in COPD

Cited by 114 publications

References 45 publications

Matrix Remodeling in Pulmonary Fibrosis and Emphysema

Matrix Remodeling in Pulmonary Fibrosis and Emphysema

Lung Extracellular Matrix and Fibroblast Function

Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts

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