Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Compr Physiol. 2013 Jan;3(1):315-30. doi: 10.1002/cphy.c120016.
Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver that control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary cause of iron-related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver-derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely, the heart and pancreas from iron-induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma.
铁是一种必需的营养物质，其含量受到严格调控。肝脏的主要功能之一是调节铁的动态平衡。肝脏可以感知全身铁需求的变化，并以强大而迅速的方式调节铁浓度。过去 10 年的研究发现了肝脏中几个控制铁调节基因表达、储存能力和铁动员的调节机制。这些功能的失调会导致铁失衡，这是铁相关疾病的主要原因。贫血和铁过载是全球最常见的两种疾病，影响超过 10 亿人。已经鉴定出肝脏来源的基因突变，证明了肝脏在铁稳态中的核心作用。在铁过量的情况下，肝脏会增加铁的储存并保护其他组织，如心脏和胰腺免受铁诱导的细胞损伤。然而，肝脏铁储存的慢性增加会导致过量的活性氧产生和肝损伤。过多的肝脏铁是导致脂肪性肝炎、纤维化、肝硬化和肝细胞癌增加的主要机制之一。
