Bronchial Airway Epithelial Cell Damage Following Exposure to Cigarette Smoke Includes Disassembly of Tight Junction Components Mediated by the Extracellular Signal-Regulated Kinase 1/2 Pathway

Petecchia, Loredana; Sabatini, Federica; Varesio, Luigi; Camoirano, Anna; Usai, Cesare; Pezzolo, Annalisa; Rossi, Giovanni A.

doi:10.1378/chest.08-1780

Cited by 92 publications

(75 citation statements)

References 51 publications

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“…Consistent with these findings, Shaykhiev et al (54) recently showed that a profound down-regulation of the entire molecular AJC machinery, particularly claudin and E-cadherin, is observed in healthy smokers when compared with nonsmokers. Our results are also in agreement with a previous report indicating that CigS extract in BEAS-2B and 16HBE14o cell lines facilitates allergen penetration by increasing epithelial permeability (54,65).…”

Section: Discussionsupporting

confidence: 94%

Hyaluronan and Layilin Mediate Loss of Airway Epithelial Barrier Function Induced by Cigarette Smoke by Decreasing E-cadherin

Forteza

Casalino‐Matsuda

Falcon

et al. 2012

Journal of Biological Chemistry

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Background: Cigarette smoke (CigS) induces hyaluronan fragmentation and increases epithelial permeability. Results: CigS and HA fragments decrease E-cadherin expression that is prevented by knocking down layilin. Conclusion: HA fragments bind to layilin and signal through RhoA/ROCK to inhibit E-cadherin. Significance: Airway epithelium is our first line of defense against inhaled insults. HA fragments released by CigS disrupt this barrier.

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Section: Discussionsupporting

confidence: 94%

Hyaluronan and Layilin Mediate Loss of Airway Epithelial Barrier Function Induced by Cigarette Smoke by Decreasing E-cadherin

Forteza

Casalino‐Matsuda

Falcon

et al. 2012

Journal of Biological Chemistry

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“…33 Intriguingly, a similar EGFR-dependent mechanism was also found to mediate the damaging effects of CS on TJs, and this event was completely abolished in the presence of AG1478. 34 These results demonstrate EGFR's essential role in mediating the damaging effects of CS on cell-cell adhesion. Whether EGFR acts alone or in combination with other cell surface receptors will require further exploration.…”

Section: Discussionmentioning

confidence: 79%

Cigarette Smoke Induces Epidermal Growth Factor Receptor-Dependent Redistribution of Apical MUC1 and Junctional β-Catenin in Polarized Human Airway Epithelial Cells

Chen

Gallup

Nikulina

et al. 2010

The American Journal of Pathology

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Cigarette smoke (CS) accounts for nearly 90% of lung cancer deaths worldwide; however, an incomplete understanding of how CS initiates preneoplastic changes in the normal airway hinders early diagnosis. Short-term exposure to CS causes aberrant activation of epidermal growth factor receptor (EGFR) and canonical Wnt/␤-catenin signaling pathways in human bronchial epithelial (HBE) cells. We hypothesize that this response is elicited through the disruption of spatially segregated cell membrane proteins in the polarized airway epithelium. Using an in vitro model of highly differentiated HBE cells, we observed membrane characteristics consistent with the native airway, including the presence of a membrane mucin, MUC1, at the apical cell pole, ␤-catenin at the apicallateral membrane, and EGFR at the basolateral membrane. Following exposure to smoke, intercellular spaces enlarge and cilia disappear. This histopathology is accompanied by molecular events that include perinuclear trafficking of basolateral EGFR, EGFR phosphorylation, pEGFR-mediated phosphorylation of MUC1's cytoplasmic tail (CT), loss of E-cadherin/␤-catenin complexes at the adherens junctions (AJs), intracellular formation and nuclear shuffling of ␤-catenin/MUC1-CT complexes, and, ultimately, upregulation and nuclear localization of Wnt nuclear effector, Lef-1. In the presence of EGFR inhibitor, AG1478, CS-induced histopathology and molecular events were inhibited. These data point to EGFR as a portal through which CS mediates its damaging effects on AJ-mediated cell polarity and activation of canonical Wnt/␤-catenin signaling.

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“…Although several studies have identified characteristics of EMT in exposed cells, such as extracellular signal-regulated kinase phosphorylation, morphological changes, and loss of epithelial junctions (13,43), EMT due to PM exposure are not prevalent in the literature. However, several EMT triggers are activated by oxidative stress, including SNAI1, p38, and hypoxia-inducible factor (44)(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Radical-Containing Ultrafine Particulate Matter Initiates Epithelial-to-Mesenchymal Transitions in Airway Epithelial Cells

Thevenot

Saravia

Jin

et al. 2013

Am J Respir Cell Mol Biol

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Environmentally persistent free radicals (EPFRs) in combustiongenerated particulate matter (PM) are capable of inducing pulmonary pathologies and contributing to the development of environmental asthma. In vivo exposure of infant rats to EPFRs demonstrates their ability to induce airway hyperresponsiveness to methacholine, a hallmark of asthma. However, the mechanisms by which combustionderived EPFRs elicit in vivo responses remain elusive. In this study, we used a chemically defined EPFR consisting of approximately 0.2 mm amorphrous silica containing 3% cupric oxide with the organic pollutant 1,2-dichlorobenzene (DCB-230). DCB-230 possesses similar radical content to urban-collected EPFRs but offers several advantages, including lack of contaminants and chemical uniformity. DCB-230 was readily taken up by BEAS-2B and at high doses (200 mg/cm 2 ) caused substantial necrosis. At low doses (20 mg/cm 2 ), DCB-230 particles caused lysosomal membrane permeabilization, oxidative stress, and lipid peroxidation within 24 hours of exposure. During this period, BEAS-2B underwent epithelial-to-mesenchymal transition (EMT), including loss of epithelial cell morphology, decreased E-cadherin expression, and increased a-smooth muscle actin (a-SMA) and collagen I production. Similar results were observed in neonatal air-liquid interface culture (i.e., disruption of epithelial integrity and EMT). Acute exposure of infant mice to DCB-230 resulted in EMT, as confirmed by lineage tracing studies and evidenced by coexpression of epithelial E-cadherin and mesenchymal a-SMA proteins in airway cells and increased SNAI1 expression in the lungs. EMT in neonatal mouse lungs after EPFR exposure may provide an explanation for epidemiological evidence supporting PM exposure and increased risk of asthma.Keywords: particulate matter; epithelial-mesenchymal transition; environmental asthma; pediatric Combustion-generated particulate matter (PM) from industrial processes and burning of biomass and fossil fuels has been linked with adverse pulmonary health effects (1). Environmental PM, both fine and ultrafine, is capable of airway deposition, alveolar penetration, respiratory distress, and exacerbation of preexisting pulmonary conditions. Previous studies highlight the potential roles of PM exposure in predisposing to asthma and pulmonary fibrosis (2-4). Additionally, PM has adjuvant effects when combined with innocuous antigen (5-7) and induces cellular damage, stimulating fibrotic remodeling in adult rodent exposure models (2). The developing pulmonary and immune systems are particularly vulnerable (8). We have developed a model for studying particulate exposures in neonatal rodents (, 7 d of age) (9), which we apply here to understand the effects of combustiongenerated environmentally persistent free radicals (EPFRs) on pulmonary airway remodeling.Delineation of the influences of particulate burden from the reactive chemical species complexed with the particulate has proven difficult. The nature of the chemical species drastically influences ...

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Bronchial Airway Epithelial Cell Damage Following Exposure to Cigarette Smoke Includes Disassembly of Tight Junction Components Mediated by the Extracellular Signal-Regulated Kinase 1/2 Pathway

Cited by 92 publications

References 51 publications

Hyaluronan and Layilin Mediate Loss of Airway Epithelial Barrier Function Induced by Cigarette Smoke by Decreasing E-cadherin

Hyaluronan and Layilin Mediate Loss of Airway Epithelial Barrier Function Induced by Cigarette Smoke by Decreasing E-cadherin

Cigarette Smoke Induces Epidermal Growth Factor Receptor-Dependent Redistribution of Apical MUC1 and Junctional β-Catenin in Polarized Human Airway Epithelial Cells

Radical-Containing Ultrafine Particulate Matter Initiates Epithelial-to-Mesenchymal Transitions in Airway Epithelial Cells

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