Citation

BibTex format

@article{Patel:2018:10.1126/scitranslmed.aaq0693,
author = {Patel, D and Peiro, T and Shoemark, A and Akthar, S and Walker, S and Grabiec, A and Jackson, P and Hussell, T and Gaggar, A and Xu, X and Trevor, J and Li, J and Steele, C and Tavernier, G and Blalock, JE and Niven, R and Gregory, L and Simpson, A and Lloyd, C and Snelgrove, RJ},
doi = {10.1126/scitranslmed.aaq0693},
journal = {Science Translational Medicine},
title = {An extracellular matrix fragment drives epithelial remodeling and airway hyper-responsiveness},
url = {http://dx.doi.org/10.1126/scitranslmed.aaq0693},
volume = {10},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - It is anticipated that bioactive fragments of the extracellular matrix (matrikines) can influence the development and progression of chronic diseases. The enzyme leukotriene A4 hydrolase (LTA4H) mediates opposing proinflammatory and anti-inflammatory activities, through the generation of leukotriene B4 (LTB4) and degradation of proneutrophilic matrikine Pro-Gly-Pro (PGP), respectively. We show that abrogation of LTB4 signaling ameliorated inflammation and airway hyperresponsiveness (AHR) in a murine asthma model, yet global loss of LTA4H exacerbated AHR, despite the absence of LTB4. This exacerbated AHR was attributable to a neutrophil-independent capacity of PGP to promote pathological airway epithelial remodeling. Thus, we demonstrate a disconnect between airway inflammation and AHR and the ability of a matrikine to promote an epithelial remodeling phenotype that negatively affects lung function. Subsequently, we show that substantial quantities of PGP are detectable in the sputum of moderate-severe asthmatics in two distinct cohorts of patients. These studies have implications for our understanding of remodeling phenotypes in asthma and may rationalize the failure of LTA4H inhibitors in the clinic.
AU - Patel,D
AU - Peiro,T
AU - Shoemark,A
AU - Akthar,S
AU - Walker,S
AU - Grabiec,A
AU - Jackson,P
AU - Hussell,T
AU - Gaggar,A
AU - Xu,X
AU - Trevor,J
AU - Li,J
AU - Steele,C
AU - Tavernier,G
AU - Blalock,JE
AU - Niven,R
AU - Gregory,L
AU - Simpson,A
AU - Lloyd,C
AU - Snelgrove,RJ
DO - 10.1126/scitranslmed.aaq0693
PY - 2018///
SN - 1946-6234
TI - An extracellular matrix fragment drives epithelial remodeling and airway hyper-responsiveness
T2 - Science Translational Medicine
UR - http://dx.doi.org/10.1126/scitranslmed.aaq0693
UR - http://hdl.handle.net/10044/1/62922
VL - 10
ER -