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Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP-10 and MET

Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP-10 and MET
Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP-10 and MET
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 inpatients 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 MMP10 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 MMP10 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.
0105-4538
Kuo, Chih-Hsi
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Pavlidis, Stelios
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Zhu, Jie Zhu
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Loza, Matthew
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Baribaud, Fred
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Rowe, Anthony
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Pandis, Ioannis
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Gibeon, David
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Hoda, Uruj
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Sousa, Ana
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Wilson, Susan
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Howarth, Peter
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Shaw, Dominick
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Fowler, Stephen
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Dahlen, Barbro
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Chanez, Pascal
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Krug, Norbert
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Sandstrom, Thomas
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Fleming, Louise
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Corfield, Julie
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Auffray, Charles
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Djukanovic, Ratko
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Sterk, Peter J.
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Guo, Yike
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Adcock, Ian M.
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Chung, Kian Fan
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U‐BIOPRED Project Team
Kuo, Chih-Hsi
bd269315-3c2d-4ee2-9788-2e05cd1d8dc0
Pavlidis, Stelios
a55dd676-c0e0-4341-9eeb-0c7990fa11c6
Zhu, Jie Zhu
20cdf53f-f452-462f-83ab-ab2c35fce827
Loza, Matthew
23f88c0f-d43b-427a-ae57-1ece2cc99b46
Baribaud, Fred
462d7940-2a64-42ba-b274-45f909e7eb04
Rowe, Anthony
d44937eb-22c1-4eee-af96-7777d804a639
Pandis, Ioannis
afdf91be-adad-4ae5-b2d2-c85ef9703281
Gibeon, David
aa0b0d08-65f2-441a-ba40-dab315b30fcf
Hoda, Uruj
141ebe74-9039-48b9-81af-cf43b33a05a8
Sousa, Ana
e6a9e34f-4190-42dc-8ac5-e870923f2cac
Wilson, Susan
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Howarth, Peter
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Shaw, Dominick
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Fowler, Stephen
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Dahlen, Barbro
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Chanez, Pascal
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Krug, Norbert
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Sandstrom, Thomas
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Fleming, Louise
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Corfield, Julie
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Auffray, Charles
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Djukanovic, Ratko
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Sterk, Peter J.
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Guo, Yike
cfbd0941-00a1-4175-bf85-ef00a1b449d2
Adcock, Ian M.
4670ebac-449c-4257-ba78-bc27d3725394
Chung, Kian Fan
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Kuo, Chih-Hsi, Pavlidis, Stelios, Zhu, Jie Zhu, Loza, Matthew, Baribaud, Fred, Rowe, Anthony, Pandis, Ioannis, Gibeon, David, Hoda, Uruj, Sousa, Ana, Wilson, Susan, 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. and Chung, Kian Fan , U‐BIOPRED Project Team (2019) Contribution of airway eosinophils in airway wall remodeling in asthma: Role of MMP-10 and MET. Allergy. (doi:10.1111/all.13727).

Record type: Article

Abstract

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 inpatients 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 MMP10 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 MMP10 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.

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e-pub ahead of print date: 22 January 2019
Published date: 12 February 2019

Identifiers

Local EPrints ID: 428241
URI: https://eprints.soton.ac.uk/id/eprint/428241
ISSN: 0105-4538
PURE UUID: 38d3b1ed-6233-49b6-823e-eeb279522355
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 18 Feb 2019 17:30
Last modified: 19 Jul 2019 16:41

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Contributors

Author: Chih-Hsi Kuo
Author: Stelios Pavlidis
Author: Jie Zhu Zhu
Author: Matthew Loza
Author: Fred Baribaud
Author: Anthony Rowe
Author: Ioannis Pandis
Author: David Gibeon
Author: Uruj Hoda
Author: Ana Sousa
Author: Susan Wilson
Author: Peter Howarth
Author: Dominick Shaw
Author: Stephen Fowler
Author: Barbro Dahlen
Author: Pascal Chanez
Author: Norbert Krug
Author: Thomas Sandstrom
Author: Louise Fleming
Author: Julie Corfield
Author: Charles Auffray
Author: Peter J. Sterk
Author: Yike Guo
Author: Ian M. Adcock
Author: Kian Fan Chung

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