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Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP ‐10 and MET
Author(s) -
Kuo ChihHsi S.,
Pavlidis Stelios,
Zhu Jie,
Loza Matthew,
Baribaud Fred,
Rowe Anthony,
Pandis Ioannis,
Gibeon David,
Hoda Uruj,
Sousa Ana,
Wilson Susan J.,
Howarth Peter,
Shaw Dominick,
Fowler Stephen,
Dahlen Barbro,
Chanez Pascal,
Krug Norbert,
Sandstrom Thomas,
Fleming Louise,
Corfield Julie,
Auffray Charles,
Djukanovic Ratko,
Sterk Peter J.,
Guo Yike,
Adcock Ian M.,
Chung Kian Fan
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13727
Subject(s) - eosinophil , chemokine , immunology , periostin , eosinophilia , medicine , eotaxin , extracellular matrix , immunohistochemistry , asthma , airway , inflammation , pathology , biology , microbiology and biotechnology , surgery
Background Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma. Methods We analyzed the transcriptomic data from bronchial biopsies of 81 patients with moderate‐to‐severe asthma of the U‐ BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA . Transcription binding site analysis used the PRIMA algorithm. Localization of proteins was by immunohistochemistry. Results Using stringent false discovery rate analysis, MMP ‐10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils ( HE ) compared to low mucosal eosinophil ( LE ) numbers. Immunohistochemical analysis confirmed increased expression of MMP ‐10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less‐stringent conditions (raw P ‐value < 0.05, log2 fold change > 0.5), we defined a 73‐gene set characteristic of the HE compared to the LE group. Thirty‐three of 73 genes drove the pathway annotation that included extracellular matrix ( ECM ) organization, mast cell activation, CC ‐chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors, and microtubule bundle formation pathways. Genes including MET and MMP 10 involved in ECM organization correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS ‐1 and SOX family proteins, that showed positive correlation with MMP 10 and MET expression. Conclusion Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP ‐10 likely play an important role in these processes.