The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Down-regulation of the Notch Pathway in Human Airway Epithelium in Association with Smoking and Chronic Obstructive Pulmonary Disease
Open accessAbstract
RATIONALE: The airway epithelium of smokers is subject to a variety of mechanisms of injury with consequent modulation of epithelial regeneration and disordered differentiation. Several signaling pathways, including the Notch pathway, control epithelial differentiation in lung morphogenesis, but little is known about the role of these pathways in adults. OBJECTIVES: We tested the hypotheses that Notch-related genes are expressed in the normal nonsmoker small airway epithelium of human adults, and that Notch-related gene expression is down-regulated in healthy smokers and smokers with chronic obstructive pulmonary disease (COPD). METHODS: We used microarray technology to evaluate the expression of 55 Notch-related genes in the small airway epithelium of nonsmokers. We used TaqMan quantitative polymerase chain reaction (PCR) to confirm the expression of key genes and we used immunohistochemistry to assess the expression of Notch-related proteins in the airway epithelium. Changes in expression of Notch genes in healthy smokers and smokers with COPD compared with nonsmokers were evaluated by PCR. MEASUREMENTS AND MAIN RESULTS: Microarray analysis demonstrated that 45 of 55 Notch-related genes are expressed in the small airway epithelium of adults. TaqMan PCR confirmed the expression of key genes with highest expression of the ligand DLL1, the receptor NOTCH2, and the downstream effector HES1. Immunohistochemistry demonstrated the expression of Jag1, Notch2, Hes1, and Hes5 in airway epithelium. Several Notch ligands, receptors, and downstream effector genes were down-regulated in smokers, with more genes down-regulated in smokers with COPD than in healthy smokers. CONCLUSIONS: These observations are consistent with the hypothesis that the Notch pathway likely plays a role in the human adult airway epithelium, with down-regulation of Notch pathway gene expression in association with smoking and COPD.
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Vestbo, J., Hurd, S. S., Agustí, A. G., Jones, P. W., Vogelmeier, C., Anzueto, A., Barnes, P. J., Fabbri, L. M., Martinez, F. J., Nishimura, M., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201204-0596pp · Cited by 15,983
Cited by
Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling
Rock, J. R., Randell, S. H., & Hogan, B. L. M. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.006031 · Cited by 730
Notch-Dependent Differentiation of Adult Airway Basal Stem Cells
Rock, J. R., Gao, X., Xue, Y., Randell, S. H., Kong, Y.-Y., & Hogan, B. L. M. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2011.04.003 · Cited by 465
Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2
Cai, G., Bossé, Y., Xiao, F., Kheradmand, F., & Amos, C. I. (2020) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202003-0693le · Cited by 322
Chilosi, M., Carloni, A., Rossi, A., & Poletti, V. (2013) · Translational Research · doi:10.1016/j.trsl.2013.06.004 · Cited by 317
At the Root: Defining and Halting Progression of Early Chronic Obstructive Pulmonary Disease
Martinez, F. J., Han, M. K., Allinson, J. P., Barr, R. G., Boucher, R. C., Calverley, P. M. A., Celli, B. R., Christenson, S. A., Crystal, R. G., Fagerås, M., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201710-2028pp · Cited by 282
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Metadata
- Authors
- Tilley, A. E., Harvey, B.-G., Heguy, A., Hackett, N. R., Wang, R., O'Connor, T. P., & Crystal, R. G.
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-03-15
- Volume
- 179
- Issue
- 6
- Pages
- 457-466
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2143060159
- Cited by
- 192
- References
- 1
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- green
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- Tilley, A. E., Harvey, B.-G., Heguy, A., Hackett, N. R., Wang, R., O'Connor, T. P., & Crystal, R. G. (2009). Down-regulation of the Notch Pathway in Human Airway Epithelium in Association with Smoking and Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.200705-795oc
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