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

EBioMedicine
Joana NevesMartina U Muckenthaler

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.

Citations

Feb 20, 2019·Histochemistry and Cell Biology·Douglas J Taatjes, Jürgen Roth
Jun 9, 2020·The Journal of Pathology·Patricia P Ogger, Adam J Byrne
Feb 20, 2019·Pharmaceuticals·Vida ZhangAirie Kim
Jul 1, 2020·Physiological Reports·Vida ZhangAirie Kim
Feb 23, 2020·The Journal of Pathology·Md Khadem AliJay C Horvat
Nov 2, 2017·Frontiers in Physiology·Jean-Christophe DescheminSophie Vaulont
Jan 6, 2019·Pharmaceuticals·Joana NevesMartina U Muckenthaler
Jan 31, 2020·JCI Insight·Nathan C WinnAlyssa H Hasty
Sep 19, 2020·American Journal of Hematology·Katarzyna Mleczko-Sanecka, Laura Silvestri
Oct 11, 2020·Biomolecules·Karolina KrzywoszyńskaHenryk Kozłowski
Sep 23, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth PerezSuzanne M Cloonan
Feb 2, 2021·Frontiers in Physiology·Oriana MarquesMartina U Muckenthaler
Apr 4, 2021·International Journal of Molecular Sciences·Elena GammellaStefania Recalcati
May 5, 2021·American Journal of Respiratory Cell and Molecular Biology·Alexandra C Brown, Jay C Horvat
Aug 28, 2021·International Journal of Molecular Sciences·Christina MertensMichaela Jung
Sep 10, 2021·Antioxidants & Redox Signaling·Hassan Mustafa ArifRui Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
protein assay
Assay
Bronchoalveolar Lavage
ELISA
flow cytometry
FACS

Software Mentioned

Nikon NIS
NIS
- Elements
Elements Viewer
GraphPad
Nikon
Flexivent
newCAST stereology
Prism

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Related Papers

Journal of Gastroenterology and Hepatology
Lawrie W Powell
JAAPA : Official Journal of the American Academy of Physician Assistants
Denise Rizzolo, Mona M Sedrak
© 2022 Meta ULC. All rights reserved