Imperial College London
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DrLouiseFleming

Faculty of Medicine, National Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7352 8121 ext 2938l.fleming

 
 
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Location

 

Department of Respiratory PaediaRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kuo:2019:10.1111/all.13727,
author = {Kuo, C-HS and Pavlidis, S and Zhu, J and Loza, M and Baribaud, F and Rowe, A and Pandis, I and Gibeon, D and Hoda, U and Sousa, A and Wilson, SJ and Howarth, P and Shaw, D and Fowler, S and Dahlen, B and Chanez, P and Krug, N and Sandstrom, T and Fleming, L and Corfield, J and Auffray, C and Djukanovic, R and Sterk, PJ and Guo, Y and Adcock, IM and Chung, KF and U-BIOPRED, Project Team},
doi = {10.1111/all.13727},
journal = {Allergy},
pages = {1102--1112},
title = {Contribution of airway eosinophils in airway wall remodeling in asthma: role of MMP-10 and MET},
url = {http://dx.doi.org/10.1111/all.13727},
volume = {74},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundEosinophils 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.MethodsWe analyzed the transcriptomic data from bronchial biopsies of 81 patients with moderatetosevere asthma of the UBIOPRED 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.ResultsUsing stringent false discovery rate analysis, MMP10 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 MMP10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using lessstringent conditions (raw Pvalue < 0.05, log2 fold change > 0.5), we defined a 73gene set characteristic of the HE compared to the LE group. Thirtythree of 73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CCchemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors, and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organization correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS1 and SOX family proteins, that showed positive correlation with MMP10 and MET expression.ConclusionPathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP10 likely play an important role in these processes.
AU  - Kuo,C-HS
AU  - Pavlidis,S
AU  - Zhu,J
AU  - Loza,M
AU  - Baribaud,F
AU  - Rowe,A
AU  - Pandis,I
AU  - Gibeon,D
AU  - Hoda,U
AU  - Sousa,A
AU  - Wilson,SJ
AU  - Howarth,P
AU  - Shaw,D
AU  - Fowler,S
AU  - Dahlen,B
AU  - Chanez,P
AU  - Krug,N
AU  - Sandstrom,T
AU  - Fleming,L
AU  - Corfield,J
AU  - Auffray,C
AU  - Djukanovic,R
AU  - Sterk,PJ
AU  - Guo,Y
AU  - Adcock,IM
AU  - Chung,KF
AU  - U-BIOPRED,Project Team
DO  - 10.1111/all.13727
EP  - 1112
PY  - 2019///
SN  - 0105-4538
SP  - 1102
TI  - Contribution of airway eosinophils in airway wall remodeling in asthma: role of MMP-10 and MET
T2  - Allergy
UR  - http://dx.doi.org/10.1111/all.13727
UR  - http://hdl.handle.net/10044/1/67192
VL  - 74
ER  -
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