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We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the transcriptomic data from bronchial biopsies of 81 patients with moderate\u2010to\u2010severe asthma of the U\u2010<jats:styled-content style=\"fixed-case\">BIOPRED<\/jats:styled-content> cohort. Expression profiling was performed using Affymetrix arrays on total <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. Transcription binding site analysis used the <jats:styled-content style=\"fixed-case\">PRIMA<\/jats:styled-content> algorithm. Localization of proteins was by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using stringent false discovery rate analysis, <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201010 and <jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content> were significantly overexpressed in biopsies with high mucosal eosinophils (<jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>) compared to low mucosal eosinophil (<jats:styled-content style=\"fixed-case\">LE<\/jats:styled-content>) numbers. Immunohistochemical analysis confirmed increased expression of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201010 and <jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content> in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less\u2010stringent conditions (raw <jats:italic>P<\/jats:italic>\u2010value\u00a0&lt;\u00a00.05, log2 fold change\u00a0&gt;\u00a00.5), we defined a 73\u2010gene set characteristic of the <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content> compared to the <jats:styled-content style=\"fixed-case\">LE<\/jats:styled-content> group. Thirty\u2010three of 73 genes drove the pathway annotation that included extracellular matrix (<jats:styled-content style=\"fixed-case\">ECM<\/jats:styled-content>) organization, mast cell activation, <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>\u2010chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors, and microtubule bundle formation pathways. Genes including <jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>10 involved in <jats:styled-content style=\"fixed-case\">ECM<\/jats:styled-content> organization correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, <jats:styled-content style=\"fixed-case\">ETS<\/jats:styled-content>\u20101 and <jats:styled-content style=\"fixed-case\">SOX<\/jats:styled-content> family proteins, that showed positive correlation with <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>10 and <jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. <jats:styled-content style=\"fixed-case\">MET<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u201010 likely play an important role in these processes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13727","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T02:06:27Z","timestamp":1548295587000},"page":"1102-1112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Contribution of airway eosinophils in airway wall remodeling in asthma: Role of <i><scp>MMP<\/scp>\u201010<\/i> and <i><scp>MET<\/scp><\/i>"],"prefix":"10.1111","volume":"74","author":[{"given":"Chih\u2010Hsi S.","family":"Kuo","sequence":"first","affiliation":[{"name":"Airways Disease National Heart &amp; Lung Institute Imperial College London UK"},{"name":"Biomedical Research Unit Royal Brompton &amp; Harefield NHS Trust London UK"},{"name":"Department of Computing &amp; Data Science Institute Imperial College London 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