| Autor: |
Heidler, Juliana, Fysikopoulos, Athanasios, Wempe, Frank, Seimetz, Michael, Bangsow, Thorsten, Tomasovic, Ana, Veit, Florian, Scheibe, Susan, Pichl, Alexandra, Weisel, Friederike, Lloyd, K. C. Kent, Jaksch, Peter, Klepetko, Walter, Weißmann, Norbert, Melchner, Harald von |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
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| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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