Joan & Sanford I. Weill Medical College of Cornell University
How Genes Influence Development of Cigarette Smoke-Induced COPD
Prolonged exposure to cigarette smoke is the greatest risk factor for the development of COPD but emerging research suggests that genetic predisposition may also influence its development. We have previously shown that patients with a mutation in the gene Irp2 have increased levels of a protein called iron regulatory protein 2 and so, are more susceptible to cigarette smoke-induced COPD. Mice lacking the protein are protected from cigarette smoke-induced COPD. Using innovative experimental models of COPD, we will study how Irp2 and iron regulate responses of the lung to cigarette smoke. The findings may be useful in identifying therapeutic targets in COPD.
Update: We have found that Irp2 promotes the accumulation of iron inside the mitochondria of lung cells, which in turn promotes dysfunction of the mitochondria. This may lead to increased responses to cigarette smoke. Targeting iron using deferiprone, a drug that binds to iron and removes it from mitochondria, alleviates the inflammation and lung injury associated with cigarette smoke. This study strongly supports the use of agents that remove iron from mitochondria as novel therapeutic approaches for COPD.