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AuthorEl-Hashim, Ahmed Z
AuthorKhajah, Maitham A
AuthorBabyson, Rhema S
AuthorRenno, Waleed M
AuthorEzeamuzie, Charles I
AuthorBenter, Ibrahim F
AuthorAkhtar, Saghir
Available date2019-12-12T11:13:34Z
Publication Date2019-11
Publication NamePLoS ONEen_US
Identifierhttp://dx.doi.org/10.1371/journal.pone.0224163
CitationEl-Hashim AZ, Khajah MA, Babyson RS, Renno WM, Ezeamuzie CI, Benter IF, et al. (2019) Ang-(1-7)/ MAS1 receptor axis inhibits allergic airway inflammation via blockade of Src-mediated EGFR transactivation in a murine model of asthma. PLoS ONE 14(11): e0224163. https://doi.org/10.1371/journal.pone.0224163
URIhttp://hdl.handle.net/10576/12393
AbstractThe angiotensin-(1-7) [Ang-(1-7)]/MAS1 receptor signaling axis is a key endogenous anti-inflammatory signaling pathway. However, the mechanisms by which its mediates the anti-inflammatory effects are not completely understood. Using an allergic murine model of asthma, we investigated whether Ang-1(1-7)/MAS1 receptor axis a): inhibits allergic inflammation via modulation of Src-dependent transactivation of the epidermal growth factor receptor (EGFR) and downstream signaling effectors such as ERK1/2, and b): directly inhibits neutrophil and/or eosinophil chemotaxis ex vivo. Ovalbumin (OVA)-induced allergic inflammation resulted in increased phosphorylation of Src kinase, EGFR, and ERK1/2. In addition, OVA challenge increased airway cellular influx, perivascular and peribronchial inflammation, fibrosis, goblet cell hyper/metaplasia and airway hyperresponsiveness (AHR). Treatment with Ang-(1-7) inhibited phosphorylation of Src kinase, EGFR, ERK1/2, the cellular and histopathological changes and AHR. Ang-(1-7) treatment also inhibited neutrophil and eosinophil chemotaxis ex vivo. These changes were reversed following pre-treatment with A779. These data show that the anti-inflammatory actions of Ang-(1-7)/ MAS1 receptor axis are mediated, at least in part, via inhibition of Src-dependent transactivation of EGFR and downstream signaling molecules such as ERK1/2. This study therefore shows that inhibition of the Src/EGRF/ERK1/2 dependent signaling pathway is one of the mechanisms by which the Ang-(1-7)/ MAS1 receptor axis mediates it anti-inflammatory effects in diseases such as asthma.
SponsorThis study was supported by Kuwait University Research Sector - grant # PT01/12. Parts of this work were supported by the research grant # SRUL02/12 to the Research Unit for Genomics, Proteomics and Cellomics Studies through the Research Core Facility. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Languageen
PublisherPLoS ONE
SubjectRAAS
SubjectAsthma
SubjectEGFR
SubjectAng-(1-7)
TitleAng-(1-7)/ MAS1 receptor axis inhibits allergic airway inflammation via blockade of Src-mediated EGFR transactivation in a murine model of asthma.
TypeArticle
Issue Number11
Volume Number14


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