Journal article

Publication year: 2013

Pages: 242-249

Journal: The Journal of Pathology

Volume number: 229

Issue number: 2

ISSN: 0022-3417

eISSN: 1096-9896

Open access status: Bronze

DOI Link: https://doi.org/10.1002/path.4127

Publisher: Wiley

Abstract: 
Pulmonary fibrosis is a devastating and progressive parenchymal lung disease with an extremely poor prognosis. Patients suffering from idiopathic pulmonary fibrosis (IPF) display a compromised lung function alongside pathophysiological features such as highly increased production of extracellular matrix, alveolar epithelial cell dysfunction, and disordered fibroproliferation features that are due to a dysregulated response to alveolar injury. Under pathophysiological conditions of IPF, abnormally high concentrations of nitric oxide (NO) are found, likely a result of increased activity of the inducible nitric oxide synthase (NOS2), giving rise to products that contribute to fibrosis development. It is known that pharmacological inhibition or knockdown of NOS2 reduces pulmonary fibrosis, suggesting a role for NOS inhibitors in the treatment of fibrosis. Recent reports identified a critical enzyme, dimethylarginine dimethylaminohydrolase (DDAH), which is exceedingly active in patients suffering from IPF and in mice treated with bleomycin. An up-regulation of DDAH was observed in primary alveolar epithelial type II (ATII) cells from mice and patients with pulmonary fibrosis, where it co-localizes with NOS2. DDAH is a key enzyme that breaks down an endogenous inhibitor of NOS, asymmetric dimethylarginine (ADMA), by metabolizing it to l-citrulline and dimethylamine. DDAH was shown to modulate key fibrotic signalling cascades, and inhibition of this enzyme attenuated many features of the disease in in vivo experiments, suggesting a possible new therapeutic strategy for the treatment of patients suffering from IPF.

Harvard Citation style: Janssen, W., Pullamsetti, S., Cooke, J., Weissmann, N., Guenther, A. and Schermuly, R. (2013) The role of dimethylarginine dimethylaminohydrolase (DDAH) in pulmonary fibrosis, The Journal of Pathology, 229(2), pp. 242-249. https://doi.org/10.1002/path.4127

APA Citation style: Janssen, W., Pullamsetti, S., Cooke, J., Weissmann, N., Guenther, A., & Schermuly, R. (2013). The role of dimethylarginine dimethylaminohydrolase (DDAH) in pulmonary fibrosis. The Journal of Pathology. 229(2), 242-249. https://doi.org/10.1002/path.4127