Impaired activation of Notch-1 signaling hinders repair processes of bronchial epithelial cells exposed to cigarette smoke
| Autor: | Claudia Sangiorgi, Paola Dino, C. Di Sano, Maria Ferraro, Elisabetta Pace, Andreina Bruno, S. Di Vincenzo, Giuseppina Chiappara, Alessandro Bertani, Claudia D'Anna, Patrizio Vitulo |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Notch Apoptosis Bronchi Toxicology Flow cytometry 03 medical and health sciences 0302 clinical medicine Western blot epithelial bronchial cell medicine Humans Notch 1 Cell Proliferation biology medicine.diagnostic_test Receptors Notch Chemistry Cell growth cigarette smoke Epithelial Cells General Medicine Epithelium Proliferating cell nuclear antigen Cell biology 030104 developmental biology medicine.anatomical_structure biology.protein Tobacco Smoke Pollution Stem cell 030217 neurology & neurosurgery Intracellular Signal Transduction |
| Zdroj: | Toxicology letters 326 (2020): 61–69. doi:10.1016/j.toxlet.2020.03.006 info:cnr-pdr/source/autori:Caterina Di Sano ; Claudia D'Anna ; Maria Ferraro ; Giuseppina Chiappara; Claudia Sangiorgi; Serena Di Vincenzo; Alessandro Bertani; Patrizio Vitulo ; Andreina Bruno; Paola Dino; Elisabetta Pace/titolo:Impaired activation of Notch-1 signaling hinders repair processes of bronchial epithelial cells exposed to cigarette smoke/doi:10.1016%2Fj.toxlet.2020.03.006/rivista:Toxicology letters/anno:2020/pagina_da:61/pagina_a:69/intervallo_pagine:61–69/volume:326 |
| DOI: | 10.1016/j.toxlet.2020.03.006 |
| Popis: | Notch-1 intervenes in the reparative processes of mucosa by controlling cell proliferation, differentiation and stem cell maintenance. Cigarette smoke alters airway epithelial homeostasis. The present study explored whether: Smokers showed altered Notch-1 expression; and whether in bronchial epithelial cells (16HBE): a) cigarette smoke extracts (CSE) altered the expression of Notch-1, of its ligand Jagged-1 (Jag-1) and the nuclear translocation of Notch-1; b) Notch-1 signaling activation as well as CSE modified Ki67, PCNA, p21, IL-33 expression, cell proliferation and repair processes. Notch-1 expression was assessed in the epithelium from large airway surgical samples from non-smoker and smoker subjects by immunohistochemistry.16HBE were cultured with/without CSE and Jag-1. A Notch-1 inhibitor (DAPT) was used as control. The expression of Notch-1, Jag-1, Ki67, PCNA, p21, IL-33 and cell proliferation (by CFSE) were all assessed by flow cytometry. Notch-1 nuclear expression was evaluated by immunofluorescence and western blot analysis. Repair processes were assessed by wound assay. Smokers had cytoplasmic but not nuclear Notch-1 expression. Although CSE increased Notch-1 expression, it counteracted Notch-1 signaling activation since it reduced Jag-1 expression and Notch-1 nuclear translocation. Notch-1 signaling activation by Jag-1 increased Ki67, PCNA and repair processes but reduced intracellular IL-33 and p21 expression without affecting cell proliferation. DAPT counteracted the effects of Notch-1 activation on PCNA and IL-33. CSE increased Ki67, PCNA, p21 and IL-33 expression but reduced cell proliferation and repair processes. In conclusion, cigarette smoke exposure, limiting Notch-1 signaling activation and hindering repair processes, amplifies injury processes in bronchial epithelial cells. |
| Databáze: | OpenAIRE |
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