Idiopathic pulmonary fibrosis is characterised by gradual scarring of the lungs until they become so thickened and damaged that they can no longer exchange oxygen with the blood; patients experience extreme fatigue, weight loss, chronic cough and shortness of breath. The disease affects mainly people over the age of 50 and, although progression varies from individual to individual, there is currently no cure and many people die within 5 years of diagnosis.
Researchers working at the University of Michigan have, however, discovered that the enzyme NOX-4 plays a key role in the development of lung scarring, a finding that could lead to new treatments for pulmonary fibrosis. The NOX family of enzymes are NADPH oxidases which catalyse the reduction of O2 to reactive oxygen species. Although specific roles for the seven known NOX isoforms have not been fully elucidated, roles in host defence against pathogens and the development of atherosclerosis have been proposed, as well as roles in other physiological processes that involve reactive oxygen species. In the present study, which is published in the August 23rd online edition of Nature Medicine, the researchers found that NOX-4 is up-regulated in tissue samples from humans with idiopathic pulmonary fibrosis and also in the lungs of mice subjected to non-infectious injury. Genetic knockout of NOX-4 or treatment with an inhibitor were shown to prevent the progression of fibrosis in two mouse models of lung injury.
This is the first study that links NOX-4 to the development of pulmonary fibrosis and the team, some of whom are now at the University of Alabama, believe that their findings may lead to the development of treatments for fibrosis in other organs as well as the lung. Although it remains to be seen whether such treatment would reverse existing fibrosis, the researchers hope that it would, at least, prevent progression of the disease.