Dysfunctional ErbB2, an EGF receptor family member, hinders repair of airway epithelial cells from asthmatic patients.
Asthma
air-liquid interface culture
airway inflammation
cell proliferation
cyclin D1
epidermal growth factor receptor
epithelial cell
erythroblastosis oncogene B2
wound repair
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
18
06
2018
revised:
26
11
2018
accepted:
30
11
2018
pubmed:
15
1
2019
medline:
9
6
2020
entrez:
15
1
2019
Statut:
ppublish
Résumé
Genetic and genomic data increasingly point to the airway epithelium as critical to asthma pathogenesis. Epithelial growth factor (EGF) family members play a fundamental role in epithelial differentiation, proliferation, and repair. Although expression of erythroblastosis oncogene B2 (ErbB2) mRNA, an EGF family receptor, was reported to be lower in asthmatic patients, little is understood about its functional role. We sought to determine whether decreased ErbB2 activation in freshly isolated human airway epithelial cells (HAECs) from asthmatic patients associated with impaired wound closure in vitro. An in vitro scratch-wound model of air-liquid interface cultured and freshly isolated HAECs were compared between HAECs from healthy control subjects (HCs) and asthmatic patients in relation to ErbB2. Freshly brushed HAECs from asthmatic patients had impaired ErbB2 activation compared with those from HCs. In an in vitro scratch-wound model, HAECs from asthmatic patients showed delayed wound closure compared with HAECs from HCs. Cell proliferation, as assessed based on [ These results implicate a primary defect in the ErbB2 pathway as constraining epithelial repair processes in asthmatic patients. Restoration of homeostatic ErbB2 function should be considered a novel asthma therapeutic target.
Sections du résumé
BACKGROUND
Genetic and genomic data increasingly point to the airway epithelium as critical to asthma pathogenesis. Epithelial growth factor (EGF) family members play a fundamental role in epithelial differentiation, proliferation, and repair. Although expression of erythroblastosis oncogene B2 (ErbB2) mRNA, an EGF family receptor, was reported to be lower in asthmatic patients, little is understood about its functional role.
OBJECTIVE
We sought to determine whether decreased ErbB2 activation in freshly isolated human airway epithelial cells (HAECs) from asthmatic patients associated with impaired wound closure in vitro.
METHODS
An in vitro scratch-wound model of air-liquid interface cultured and freshly isolated HAECs were compared between HAECs from healthy control subjects (HCs) and asthmatic patients in relation to ErbB2.
RESULTS
Freshly brushed HAECs from asthmatic patients had impaired ErbB2 activation compared with those from HCs. In an in vitro scratch-wound model, HAECs from asthmatic patients showed delayed wound closure compared with HAECs from HCs. Cell proliferation, as assessed based on [
CONCLUSION
These results implicate a primary defect in the ErbB2 pathway as constraining epithelial repair processes in asthmatic patients. Restoration of homeostatic ErbB2 function should be considered a novel asthma therapeutic target.
Identifiants
pubmed: 30639343
pii: S0091-6749(19)30008-9
doi: 10.1016/j.jaci.2018.11.046
pmc: PMC6556416
mid: NIHMS1020874
pii:
doi:
Substances chimiques
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2075-2085.e10Subventions
Organisme : NCRR NIH HHS
ID : UL1 RR024153
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL069174
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL144418
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI106684
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI040600
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL109152
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
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