Σφακιανάκης Αλέξανδρος
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Παρασκευή 11 Ιανουαρίου 2019

Dysfunctional ErbB2, an EGF receptor family member, hinders repair of asthmatic airway epithelial cells

Publication date: Available online 10 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Hideki Inoue, Takeshi Hattori, Xiuxia Zhou, Emily B. Etling, Brian D. Modena, John B. Trudeau, Fernando Holguin, Sally E. Wenzel

Abstract
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. While ErbB2 mRNA, an EGF family receptor, was reported to be lower in asthma, little is understood about its functional role.

Objective

To determine whether decreased ErbB2 activation in freshly isolated asthmatic human airway epithelial cells (HAECs) 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 asthmatic and healthy HAECs in relation to ErbB2.

Results

Freshly brushed asthmatic HAECs had impaired ErbB2 activation compared to healthy controls. In an in vitro scratch wound model, asthmatic HAECs showed delayed wound closure compared to healthy HAECs. Cell proliferation, assessed by [3H] thymidine incorporation post wounding, as well as expression or activation of ErbB2 and CCND1 at the leading edge of the wound were lower in asthmatic compared to healthy HAECs. A selective ErbB2 tyrosine kinase inhibitor, mubritinib impaired wound closure and decreased CCND1 expression in healthy HAECs, with less impact on asthmatic cells, supporting diminished activity in asthma.

Conclusion

These results implicate a primary defect in the ErbB2 pathway as constraining asthmatic epithelial repair processes. Restoration of homeostatic ErbB2 function should be considered as a novel asthma therapeutic target.

Graphical abstract

Graphical abstract for this article



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