Imperial College London
Portrait Picture

DR COEN WIEGMAN

Faculty of Medicine, National Heart & Lung Institute

Senior Teaching Fellow
 
 
 
//

Contact

 

+44 (0)20 7594 1980c.wiegman

 
 
//

Location

 

305Guy Scadding BuildingRoyal Brompton Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Gao:2015:10.1042/CS20150273,
author = {Gao, W and Yuan, C and Zhang, J and Li, L and Yu, L and Wiegman, CH and Barnes, PJ and Adcock, IM and Huang, M and Yao, X},
doi = {10.1042/CS20150273},
journal = {Clinical Science},
pages = {1011--1023},
title = {Klotho expression is reduced in COPD airway epithelial cells: effects on inflammation and oxidant injury.},
url = {http://dx.doi.org/10.1042/CS20150273},
volume = {129},
year = {2015}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - COPD (chronic obstructive pulmonary disease) is associated with sustained inflammation, excessive injury, and accelerated lung aging. Human Klotho (KL) is an anti-aging protein that protects cells against inflammation and damage. In the present study, we quantified KL expression in the lungs of COPD patients and in an ozone-induced mouse model of COPD, and investigated the mechanisms that control KL expression and function in the airways. KL distribution and levels in human and mouse airways were measured by immunohistochemistry and Western blotting. The effect of CSE (cigarette smoke extract) on KL expression was detected in human bronchial epithelial cells. Moreover, the effect of KL on CSE-mediated inflammation and hydrogen peroxide-induced cellular injury/apoptosis was determined using siRNAs. KL expression was decreased in the lungs of smokers and further reduced in patients with COPD. Similarly, 6 weeks of exposure to ozone decreased KL levels in airway epithelial cells. CSE and TNFα (tumour necrosis factor α) decreased KL expression and release from airway epithelial cells, which was associated with enhanced pro-inflammatory cytokine expression. Moreover, KL depletion increased cell sensitivity to cigarette smoke-induced inflammation and oxidative stress-induced cell damage. These effects involved the NF-κB (nuclear factor κB), MAPK (mitogen-activated protein kinase) and Nrf2 (nuclear factor erythroid 2-related factor 2) pathways. Reduced KL expression in COPD airway epithelial cells was associated with increased oxidative stress, inflammation and apoptosis. These data provide new insights into the mechanisms associated with the accelerated lung aging in COPD development.
AU  - Gao,W
AU  - Yuan,C
AU  - Zhang,J
AU  - Li,L
AU  - Yu,L
AU  - Wiegman,CH
AU  - Barnes,PJ
AU  - Adcock,IM
AU  - Huang,M
AU  - Yao,X
DO  - 10.1042/CS20150273
EP  - 1023
PY  - 2015///
SN  - 0143-5221
SP  - 1011
TI  - Klotho expression is reduced in COPD airway epithelial cells: effects on inflammation and oxidant injury.
T2  - Clinical Science
UR  - http://dx.doi.org/10.1042/CS20150273
VL  - 129
ER  -
Download