Smoking Dysregulates the Human Airway Basal Cell Transcriptome at COPD Risk Locus 19q13.2

Ryan, Dorothy; Vincent, Thomas L.; Salit, Jacqueline; Walters, Matthew S.; Agosto-Perez, Francisco; Shaykhiev, Renat; Strulovici-Barel, Yael; Downey, Robert J.; Buro-Auriemma, Lauren J.; Staudt, Michelle R.; Hackett, Neil R.; Mezey, Jason G.; Crystal, Ronald G.

doi:10.1371/journal.pone.0088051

Cited by 66 publications

(59 citation statements)

References 53 publications

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“…In COPD, recent evidence suggests that basal progenitor cells, which are crucial for airway epithelial differentiation, exhibit a reduced regenerative capacity [115,116]. Similar to other cell types, stem or progenitor cells within the lung are exposed to environmental stressors and most likely exhibit cell-autonomous hallmarks of ageing, including cellular senescence, epigenetic changes and telomere attrition [117].…”

Section: Stem Cell Exhaustionmentioning

confidence: 99%

Hallmarks of the ageing lung

2015

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Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, "dysregulation of the extracellular matrix", which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases. @ERSpublications Hallmarks of ageing are selecting factors for the pathogenesis of COPD, lung cancer and IPF

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Section: Stem Cell Exhaustionmentioning

confidence: 99%

Hallmarks of the ageing lung

2015

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“…RNA sequencing of nonsmoker primary basal cells (n=10) was assessed as previously described (Ryan et al, 2014). The data are publically available at the Gene Expression Omnibus (GEO) site (http://www.ncbi.nlm.nih.gov/ geo/), accession number 64464.…”

Section: Rna Sequencingmentioning

confidence: 99%

Endothelial MMP14 is required for endothelial dependent growth support of human airway basal cells

Ding

Gomi

Rafii

et al. 2015

Journal of Cell Science

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Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying nonepithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell-endothelialcell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal 'crosstalk' between human airway basal cells and endothelial cells that regulates proliferation of basal cells.

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“…Gene Ontology analysis of the categories of the SAE waterpipe-responsive genes showed a broad distribution dominated by genes related to metabolism, signal transduction, transcription, and transport ( Figure 2C). Interestingly, while the SAE transcriptome of cigarette smokers is characterized by upregulation of many oxidative stress-related genes (13)(14)(15)(16)(17), very few genes in this category were upregulated in the SAE of waterpipe smokers (categorized as functional category "other" due to the low number of oxidant-related genes) (see DISCUSSION in the online supplement and Table E2). …”

Section: Small Airway Epitheliummentioning

confidence: 99%

“…On the basis of knowledge that the first abnormalities associated with cigarette smoking are found in lung cells long before there are abnormalities in clinical parameters such as lung function and lung imaging (12)(13)(14)(15)(16)(17), we hypothesized that even light-use waterpipe smoking for only a few years, exposing the smoker not only to tobacco smoke but also to the flavorings added to the tobacco and the volatile components of the heated charcoal surrounding the tobacco, likely mediates abnormalities relevant to lung health.…”

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confidence: 99%

Pulmonary Abnormalities in Young, Light-Use Waterpipe (Hookah) Smokers

Strulovici-Barel¹,

Shaykhiev²,

Salit³

et al. 2016

Am J Respir Crit Care Med

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Rationale: Waterpipes, also called hookahs, are currently used by millions of people worldwide. Despite the increasing use of waterpipe smoking, there is limited data on the health effects of waterpipe smoking and there are no federal regulations regarding its use.Objectives: To assess the effects of waterpipe smoking on the human lung using clinical and biological parameters in young, light-use waterpipe smokers. Methods:We assessed young, light-use, waterpipe-only smokers in comparison with lifelong nonsmokers using clinical parameters of cough and sputum scores, lung function, and chest high-resolution computed tomography as well as biological parameters of lung epithelial lining fluid metabolome, small airway epithelial (SAE) cell differential and transcriptome, alveolar macrophage transcriptome, and plasma apoptotic endothelial cell microparticles.Measurements and Main Results: Compared with nonsmokers, waterpipe smokers had more cough and sputum as well as a lower lung diffusing capacity, abnormal epithelial lining fluid metabolome profile, increased proportions of SAE secretory and intermediate cells, reduced proportions of SAE ciliated and basal cells, markedly abnormal SAE and alveolar macrophage transcriptomes, and elevated levels of apoptotic endothelial cell microparticles.Conclusions: Young, light-use, waterpipe-only smokers have a variety of abnormalities in multiple lung-related biological and clinical parameters, suggesting that even limited waterpipe use has broad consequences on human lung biology and health. We suggest that large epidemiological studies should be initiated to investigate the harmful effects of waterpipe smoking.Keywords: waterpipe; smoking; pulmonary; transcriptome; endothelial microparticlesThe waterpipe, also called hookah, shisha, or narghile, an instrument for smoking fruit-flavored tobacco, is used by millions of people worldwide (1-4). The tobacco is placed in a bowl surrounded by burning charcoal; when the smoker inhales, air is pulled through the charcoal and into the bowl holding the tobacco (3, 5). The resulting smoke is bubbled through water, carried through a hose, and inhaled. It includes volatilized and pyrolyzed tobacco products, equivalent in a single bowl waterpipe session over 45-60 minutes to one pack of cigarettes, together with carbon monoxide and charcoal components. In

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Smoking Dysregulates the Human Airway Basal Cell Transcriptome at COPD Risk Locus 19q13.2

Cited by 66 publications

References 53 publications

Hallmarks of the ageing lung

Hallmarks of the ageing lung

Endothelial MMP14 is required for endothelial dependent growth support of human airway basal cells

Pulmonary Abnormalities in Young, Light-Use Waterpipe (Hookah) Smokers

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