TY  - JOUR
A1  - Heidler, Juliana
A1  - Fysikopoulos, Athanasios
A1  - Wempe, Frank
A1  - Seimetz, Michael
A1  - Bangsow, Thorsten
A1  - Tomasovic, Ana
A1  - Veit, Florian
A1  - Scheibe, Susan
A1  - Pichl, Alexandra
A1  - Weisel, Friederike
A1  - Lloyd, K. C. Kent
A1  - Jaksch, Peter
A1  - Klepetko, Walter
A1  - Weißmann, Norbert
A1  - Melchner, Harald von
T1  - Sestrin-2, a repressor of PDGFRβ signalling, promotes cigarette-smoke-induced pulmonary emphysema in mice and is upregulated in individuals with COPD
T2  - Disease models & mechanisms
N2  - Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD is caused by chronic exposure to cigarette smoke and/or other environmental pollutants that are believed to induce reactive oxygen species (ROS) that gradually disrupt signalling pathways responsible for maintaining lung integrity. Here we identify the antioxidant protein sestrin-2 (SESN2) as a repressor of PDGFRβ signalling, and PDGFRβ signalling as an upstream regulator of alveolar maintenance programmes. In mice, the mutational inactivation of Sesn2 prevents the development of cigarette-smoke-induced pulmonary emphysema by upregulating PDGFRβ expression via a selective accumulation of intracellular superoxide anions (O2−). We also show that SESN2 is overexpressed and PDGFRβ downregulated in the emphysematous lungs of individuals with COPD and to a lesser extent in human lungs of habitual smokers without COPD, implicating a negative SESN2-PDGFRβ interrelationship in the pathogenesis of COPD. Taken together, our results imply that SESN2 could serve as both a biomarker and as a drug target in the clinical management of COPD.
KW  - COPD
KW  - KGF
KW  - PDGFRβ
KW  - ROS
KW  - Sestrin 2
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/34219
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-342195
SN  - 1754-8403
SN  - 1754-8411
N1  - Copyright © 2013. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
VL  - 6
IS  - 6
SP  - 1378
EP  - 1387
PB  - Company of Biologists Limited
CY  - Cambridge
ER  -