BibTex format
@article{Ramis:2022:10.1183/13993003.04361-2020,
author = {Ramis, J and Middlewick, R and Pappalardo, F and Cairns, JT and Stewart, ID and John, AE and Naveed, S-U-N and Krishnan, R and Miller, S and Shaw, DE and Brightling, CE and Buttery, L and Rose, F and Jenkins, G and Johnson, SR and Tatler, AL},
doi = {10.1183/13993003.04361-2020},
journal = {European Respiratory Journal},
pages = {1--13},
title = {Lysyl oxidase-like 2 is increased in asthma and contributes to asthmatic airway remodelling},
url = {http://dx.doi.org/10.1183/13993003.04361-2020},
volume = {60},
year = {2022}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Airway smooth muscle cells (ASM) are fundamental to asthma pathogenesis, influencing bronchoconstriction, airway hyper-responsiveness, and airway remodelling. Extracellular matrix (ECM) can influence tissue remodelling pathways, however, to date no study has investigated the effect of ASM ECM stiffness and crosslinking on the development of asthmatic airway remodelling. We hypothesised that TGFβ activation by ASM is influenced by ECM in asthma and sought to investigate the mechanisms involved. This study combines in vitro and in vivo approaches: human ASM cells were used in vitro to investigate basal TGFβ activation and expression of ECM crosslinking enzymes. Human bronchial biopsies from asthmatic and non-asthmatic donors were used to confirm LOXL2 expression ASM. A chronic ovalbumin model of asthma was used to study the effect of LOXL2 inhibition on airway remodelling. We found that ASM cells from asthmatics activated more TGFβ basally than non-asthmatic controls and that diseased cell-derived ECM influences levels of TGFβ activated. Our data demonstrate that the ECM crosslinking enzyme LOXL2 is increased in asthmatic ASM cells and in bronchial biopsies. Crucially, we show that LOXL2 inhibition reduces ECM stiffness and TGFβ activation in vitro, and can reduce subepithelial collagen deposition and ASM thickness, two features of airway remodelling, in an ovalbumin mouse model of asthma. These data are the first to highlight a role for LOXL2 in the development of asthmatic airway remodelling and suggest that LOXL2 inhibition warrants further investigation as a potential therapy to reduce remodelling of the airways in severe asthma.
AU - Ramis,J
AU - Middlewick,R
AU - Pappalardo,F
AU - Cairns,JT
AU - Stewart,ID
AU - John,AE
AU - Naveed,S-U-N
AU - Krishnan,R
AU - Miller,S
AU - Shaw,DE
AU - Brightling,CE
AU - Buttery,L
AU - Rose,F
AU - Jenkins,G
AU - Johnson,SR
AU - Tatler,AL
DO - 10.1183/13993003.04361-2020
EP - 13
PY - 2022///
SN - 0903-1936
SP - 1
TI - Lysyl oxidase-like 2 is increased in asthma and contributes to asthmatic airway remodelling
T2 - European Respiratory Journal
UR - http://dx.doi.org/10.1183/13993003.04361-2020
UR - https://www.ncbi.nlm.nih.gov/pubmed/34996828
UR - https://erj.ersjournals.com/content/60/1/2004361.article-info
UR - http://hdl.handle.net/10044/1/96834
VL - 60
ER -
