Hepcidin knockout mice fed with iron-rich diet develop chronic liver injury and liver fibrosis due to lysosomal iron overload

Background & Aims Hepcidin is the central regulator of iron homeostasis and altered hepcidin signalling results in both hereditary and acquired iron overload. While the association between iron overload and development of end-stage liver disease is well established, the underlying mechanisms are...

Full description

Saved in:
Bibliographic Details
Published in:Journal of hepatology 2014-09, Vol.61 (3), p.633-641
Main Authors: Lunova, Mariia, Goehring, Claudia, Kuscuoglu, Deniz, Mueller, Katrin, Chen, Yu, Walther, Paul, Deschemin, Jean-Christophe, Vaulont, Sophie, Haybaeck, Johannes, Lackner, Carolin, Trautwein, Christian, Strnad, Pavel
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Autophagy
Disease Models, Animal
Gastroenterology and Hepatology
Hemochromatosis
Hepatic Stellate Cells - pathology
Hepatic Stellate Cells - physiology
Hepcidins - deficiency
Hepcidins - genetics
Hepcidins - physiology
Homeostasis - physiology
Inflammation
Iron - metabolism
Iron, Dietary - adverse effects
Liver - enzymology
Liver - pathology
Liver Cirrhosis - etiology
Liver Cirrhosis - metabolism
Liver Cirrhosis - physiopathology
Lung Injury - etiology
Lung Injury - metabolism
Lung Injury - physiopathology
Lysosomes - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Time Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background & Aims Hepcidin is the central regulator of iron homeostasis and altered hepcidin signalling results in both hereditary and acquired iron overload. While the association between iron overload and development of end-stage liver disease is well established, the underlying mechanisms are largely unknown. To improve that, we analysed hepcidin knockout (KO) mice as a model of iron overload-associated liver disease. Methods Hepcidin wild type (WT) and KO mice fed with 3% carbonyl iron-containing diet starting at one month of age were compared to age-matched animals kept on standard chow. Liver histology and serum parameters were used to assess the extent of liver injury and fibrosis. Iron distribution was determined by subcellular fractionation and electron microscopy. Results Among mice kept on iron-rich diet, 6 months old hepcidin KO mice ( vs. WT) displayed profound hepatic iron overload (3186 ± 411 vs. 1045 ± 159 μg/mg tissue, p
ISSN:0168-8278
1600-0641
DOI:10.1016/j.jhep.2014.04.034