| First Author | Heidler J | Year | 2013 |
| Journal | Dis Model Mech | Volume | 6 |
| Issue | 6 | Pages | 1378-87 |
| PubMed ID | 24046361 | Mgi Jnum | J:202834 |
| Mgi Id | MGI:5522596 | Doi | 10.1242/dmm.013482 |
| Citation | Heidler J, et al. (2013) Sestrin-2, a repressor of PDGFRbeta signalling, promotes cigarette-smoke-induced pulmonary emphysema in mice and is upregulated in individuals with COPD. Dis Model Mech 6(6):1378-87 |
| abstractText | 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 PDGFRbeta signalling, and PDGFRbeta 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 PDGFRbeta expression via a selective accumulation of intracellular superoxide anions (O2(-)). We also show that SESN2 is overexpressed and PDGFRbeta 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-PDGFRbeta 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. |
