Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease.

Abstract

Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s) involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S), increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder.

• Authors: Joana Neves, Dominik Leitz, Simone Kraut, Christina Brandenberger, Raman Agrawal, Norbert Weissmann, Christian Mühlfeld, Marcus A Mall, Sandro Altamura, Martina U Muckenthaler
• Journal: EBioMedicine (EBioMedicine) Vol. 20 Pg. 230-239 (Jun 2017) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 28499927 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Cation Transport Proteins
• Cytokines
• Hepcidins
• metal transporting protein 1
• Iron
• Oxygen

Topics

• Animals
• Blood Gas Analysis
• Cation Transport Proteins (genetics, metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Hepcidins (genetics, metabolism)
• Iron (metabolism)
• Iron Overload (genetics, metabolism, pathology)
• Lipid Peroxidation
• Lung Diseases (genetics, metabolism, pathology, physiopathology)
• Macrophages (immunology, metabolism)
• Macrophages, Alveolar (immunology, metabolism, pathology)
• Mice
• Mice, Transgenic
• Oxygen (metabolism)
• Respiratory Function Tests