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 smokeinduced pulmonary emphysema in mice and is upregulated in patients 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 programs. 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 patients 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  - Sestrin 2
KW  - PDGFRβ
KW  - ROS
KW  - KGF
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/31650
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-316507
SN  - 1754-8403
SN  - 1754-8411
N1  - © 2013. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms, Preprint, später in: Disease models & mechanisms, 6.2013, Nr. 6, S. 1378-1387, doi:10.1242/dmm.013482
SP  - 1
EP  - 30
PB  - Company of Biologists Limited
CY  - Cambridge
ER  -