Iron Homeostasis, Hepatocellular Injury, and Fibrogenesis in Hemochromatosis: The Role of Inflammation in a Noninflammatory Liver Disease

被引:52
作者
Ramm, Grant A. [1 ]
Ruddell, Richard G. [1 ]
机构
[1] Queensland Inst Med Res, Hepat Fibrosis Grp, Brisbane, Qld 4029, Australia
基金
英国医学研究理事会;
关键词
Iron; inflammation; hepcidin; hepatic stellate cell; hepatic fibrosis; hemochromatosis; NF-KAPPA-B; MITOCHONDRIAL PERMEABILITY TRANSITION; BONE MORPHOGENETIC PROTEIN-6; ENDOPLASMIC-RETICULUM STRESS; STELLATE CELL ACTIVATION; GENE-EXPRESSION; LIPID-PEROXIDATION; OXIDATIVE STRESS; HEPCIDIN EXPRESSION; HEPATIC IRON;
D O I
10.1055/s-0030-1255356
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Iron is a crucially important element in normal cellular function and thus the regulation of iron homeostasis is tightly controlled. When this regulation is disrupted, for instance in hereditary hemochromatosis, abnormal intestinal absorption of iron leads to cellular toxicity, tissue injury, and organ fibrosis via the deposition of this iron in parenchymal cells of a number of different organs such as the heart, pancreas, and liver. Iron-generated oxyradicals contribute to the peroxidation of lipid membranes leading to organelle fragility and cellular toxicity. This process is thought to contribute to hepatocellular necrosis and/or apoptosis in the liver with the subsequent activation of hepatic stellate cells and the development of hepatic fibrosis and cirrhosis. Understanding the processes associated with normal iron homeostasis is crucially important as this will ultimately provide clues as to how altered iron uptake and delivery leads to tissue injury and organ dysfunction in diseases of disordered iron metabolism. This review highlights recent advances in identifying major regulators associated with hepatic iron homeostasis and examines the potential mechanisms involved in the development of iron overload-induced hepatic injury and fibrogenesis.
引用
收藏
页码:271 / 287
页数:17
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