Cigarette Smoke Activates NOTCH3 to Promote Goblet Cell Differentiation in Human Airway Epithelial Cells
@article{Bodas2020CigaretteSA, title={Cigarette Smoke Activates NOTCH3 to Promote Goblet Cell Differentiation in Human Airway Epithelial Cells}, author={Manish Bodas and Andrew R. Moore and Bharathiraja Subramaniyan and Constantin Georgescu and Jonathan D. Wren and Willard M. Freeman and Brent R Brown and Jordan Patrick Metcalf and Matthew S Walters}, journal={bioRxiv}, year={2020}, url={https://api.semanticscholar.org/CorpusID:220515989} }
Notch3 activation is identified as one of the important mechanisms by which cigarette smoke induces goblet cell differentiation, thus providing a novel potential strategy to control GCMH-related pathologies in smokers and patients with COPD.
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54 References
NOTCH3 contributes to rhinovirus-induced goblet cell hyperplasia in COPD airway epithelial cells
- 2018
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RV induces sustained GCH via NOTCH3 particularly in COPD cells or mice with COPD phenotype, which may be one of the mechanisms that may contribute to RV-induced prolonged airways obstruction in COPd.
Different profiles of notch signaling in cigarette smoke-induced pulmonary emphysema and bleomycin-induced pulmonary fibrosis
- 2015
Biology, Environmental Science
Different profiles of Notch signaling mediate naive T cell differentiation which might be involved in pulmonary emphysema and fibrosis, and this implies that the CS exposure but not the BLM exposure is capable of initiating NotCh signaling in lymphoid tissue of the lung, which is likely relevant to the pathogenesis of pulmonary empysema.
Down-regulation of the notch pathway in human airway epithelium in association with smoking and chronic obstructive pulmonary disease.
- 2009
Medicine
Microarray analysis demonstrated that 45 of 55 Notch-related genes are expressed in the small airway epithelium of adults, which is consistent with the hypothesis that the Notch pathway likely plays a role in the human adult airways, with down-regulation of Notch pathways gene expression in association with smoking and COPD.
EGF‐Amphiregulin Interplay in Airway Stem/Progenitor Cells Links the Pathogenesis of Smoking‐Induced Lesions in the Human Airway Epithelium
- 2017
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EGF‐AREG interplay in airway BC stem/progenitor cells is one of the mechanisms that mediates the interconnected pathogenesis of all major smoking‐induced lesions in the human airway epithelium.
SPDEF regulates goblet cell hyperplasia in the airway epithelium.
- 2007
Biology, Medicine
Mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands, and expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6.
Altered generation of ciliated cells in chronic obstructive pulmonary disease
- 2019
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The COPD airway epithelium displays altered differentiation for ciliated cells, which recapitulates in vitro, at least in part through TGF-β1, which is hypothesized to cause bronchial epithelial cell lineage specification to be dysregulated.
Notch2 is required for inflammatory cytokine-driven goblet cell metaplasia in the lung.
- 2015
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Blocking Notch3 Signaling Abolishes MUC5AC Production in Airway Epithelial Cells from Asthmatics.
- 2020
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It is demonstrated that NOTCH3 is a regulator of MUC5AC production, and increased Notch3 signaling in the asthmatic airway epithelium may therefore be an underlying driver of excess MUC 5AC production.
Notch Signaling Prevents Mucous Metaplasia in Mouse Conducting Airways during Postnatal Development
- 2011
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Notch signaling is suggested to be critical in regulating the response of the lung to environmental injurants or allergens that result in goblet cell metaplasia during postnatal life.
Cigarette smoke-induced autophagy impairment accelerates lung aging, COPD-emphysema exacerbations and pathogenesis.
- 2018
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