Delay of airway epithelial wound repair in COPD is associated with airflow obstruction severity

Perotin-Collard, Jeanne-Marie; Adam, Damien; Vella-Boucaud, Juliette; Delépine, G.; Sandu, Sebastian; Jonvel, Anne-Carole; Prévost, Alain; Berthiot, G; Pison, Christophe; Lebargy, F.; Birembaut, Philippe; Coraux, Christelle; Deslée, G.

doi:10.1186/s12931-014-0151-9

Cited by 61 publications

(56 citation statements)

References 24 publications

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“…The situation in severe COPD may be very different from the relative early stage, in which the repairing ability of BCs may be relative conserved. As Perotin et al reported that delayed rather than enhanced epithelial wound repair was found in severe COPD [42]. Actually, we agree with this idea.…”

Section: Discussionsupporting

confidence: 90%

Increased expression of TROP2 in airway basal cells potentially contributes to airway remodeling in chronic obstructive pulmonary disease

Liu

Wang

et al. 2016

Respir Res

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BackgroundThe airway epithelium of chronic obstructive pulmonary disease (COPD) patients undergoes aberrant repair and remodeling after repetitive injury following exposure to environmental factors. Abnormal airway regeneration observed in COPD is thought to originate in the stem/progenitor cells of the airway epithelium, the basal cells (BCs). However, the molecular mechanisms underlying these changes remain unknown. Here, trophoblast cell surface antigen 2 (TROP2), a protein implicated in the regulation of stem cell activity, was examined in lung tissue samples from COPD patients.MethodsThe expression of TROP2 and hyperplasia index Ki67 was assessed in lung epithelium specimens from non-smokers (n = 24), smokers (n = 24) and smokers with COPD (n = 24). Primary airway BCs were isolated by bronchoscopy from healthy individuals and COPD patients and subsequently transfected with pcDNA3.1-TROP2 or siRNA sequence in vitro. The functional consequences of TROP2 overexpression in BCs were explored.ResultsImmunohistochemistry and immunofluorescence revealed increased TROP2 expression in airway BCs in smokers with COPD compared to nonsmokers and smokers without COPD, and staining was highly localized to hyperplastic regions containing Ki67 positive cells. TROP2 expression was also inversely correlated with airflow limitation in patients with COPD (r = −0.53, P < 0.01). pcDNA3.1-TROP2-BCs in vitro exhibited improved proliferation with activation of ERK1/2 phosphorylation signaling pathway. In parallel, changes in vimentin and E-cadherin in pcDNA3.1-TROP2-BCs were consistent with an epithelial-mesenchymal transition (EMT)-like change, and secretion of inflammatory factors IL-1β, IL-8 and IL-6 was increased. Moreover, down-regulation of TROP2 by siRNA significantly attenuated the proliferation of BCs derived from COPD patients. EMT-like features and cytokine levels of COPD basal cells were also weakened following the down-regulation of TROP2.ConclusionThe results indicate that TROP2 may play a crucial role in COPD by affecting BC function and thus airway remodeling through increased BC hyperplasia, EMT-like change, and introduction of inflammatory molecules into the microenvironment.

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Section: Discussionsupporting

confidence: 90%

Increased expression of TROP2 in airway basal cells potentially contributes to airway remodeling in chronic obstructive pulmonary disease

Liu

Wang

et al. 2016

Respir Res

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“…This mechanism may be impaired in COPD, since previous studies have reported attenuated Nrf2-dependent antioxidant responses in the bronchial tissues from COPD patients compared to non-COPD smokers [27, 28]. Moreover, it has been shown that COPD airway epithelial cells display reduced wound repair and epithelial barrier properties [29, 30]. Therefore, it can be speculated that an impaired oxidative stress response is related to epithelial dysfunction during COPD disease progression.…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Modulates Repair and Innate Immunity following Injury to Airway Epithelial Cells

et al. 2016

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Cigarette smoking is the main risk factor associated with chronic obstructive pulmonary disease (COPD), and contributes to COPD development and progression by causing epithelial injury and inflammation. Whereas it is known that cigarette smoke (CS) may affect the innate immune function of airway epithelial cells and epithelial repair, this has so far not been explored in an integrated design using mucociliary differentiated airway epithelial cells. In this study, we examined the effect of whole CS exposure on wound repair and the innate immune activity of mucociliary differentiated primary bronchial epithelial cells, upon injury induced by disruption of epithelial barrier integrity or by mechanical wounding. Upon mechanical injury CS caused a delayed recovery in the epithelial barrier integrity and wound closure. Furthermore CS enhanced innate immune responses, as demonstrated by increased expression of the antimicrobial protein RNase 7. These differential effects on epithelial repair and innate immunity were both mediated by CS-induced oxidative stress. Overall, our findings demonstrate modulation of wound repair and innate immune responses of injured airway epithelial cells that may contribute to COPD development and progression.

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“…Clinical assessment and pulmonary function tests were performed. Emphysema quantification on the resected lobe was performed visually on thoracic computed tomography scan by two independent investigators as previously described [8,9]. Formalin-fixed paraffin-embedded (FFPE) lung tissues distant from the tumour were stained with haematoxylin and eosin for bronchial epithelium analysis.…”

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confidence: 99%

Alteration of primary cilia in COPD

et al. 2018

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Chronic obstructive pulmonary disease (COPD) is a major economic and social concern worldwide because of its impact on mortality and morbidity [1]. COPD is characterised by airway epithelium remodelling, a hallmark of dysregulated airway epithelium plasticity [2]. There are currently no available therapeutics to restore the integrity and functionality of the epithelium. Therefore, novel sources of investigation are becoming crucial to understand the alterations at the root of COPD initiation. Non-motile primary cilia are solitary sensor organelles playing a critical role in cell cycle control, proliferation, polarity and differentiation, particularly of ciliated cells possessing motile cilia [3, 4]. Primary cilia are assembled on different types of human cells depending on their state and activities in response to cellular quiescence where they relay extracellular signals and retract upon cell cycle re-entry [5]. Alterations of primary cilium structure and function are responsible for ciliopathies [6, 7]. Primary cilia may be crucial in determining outcomes during airway epithelial cell differentiation thus we hypothesised that primary cilia are present in adult epithelial cells and may play a key role in airway plasticity. First, we investigated the presence and localisation of primary cilia in the bronchial epithelium. Secondly, we analysed the relationships between primary cilia and clinical, functional and histological characteristics of non-COPD and COPD patients.

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Delay of airway epithelial wound repair in COPD is associated with airflow obstruction severity

Cited by 61 publications

References 24 publications

Increased expression of TROP2 in airway basal cells potentially contributes to airway remodeling in chronic obstructive pulmonary disease

Increased expression of TROP2 in airway basal cells potentially contributes to airway remodeling in chronic obstructive pulmonary disease

Cigarette Smoke Modulates Repair and Innate Immunity following Injury to Airway Epithelial Cells

Alteration of primary cilia in COPD

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