Journal
DISEASE MODELS & MECHANISMS
Volume 6, Issue 6, Pages 1378-1387Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dmm.013482
Keywords
-
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [SFB815]
- DFG [ME 820-2]
- Else Kroner-Fresenius-Stiftung [2011_A47]
- Bundesministerium fur Bildung und Forschung (NGFNplus-DiGtoP consortium) [01GS0858]
- Excellence Cluster Cardiopulmonary System (ECCPS)
- Boehringer Ingelheim Foundation
Ask authors/readers for more resources
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 PDGFR beta signalling, and PDGFR beta 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 PDGFR beta expression via a selective accumulation of intracellular superoxide anions (O-2(-)). We also show that SESN2 is overexpressed and PDGFR beta 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-PDGFR beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available