Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
PLoS One. 2009 Sep 29;4(9):e7212. doi: 10.1371/journal.pone.0007212.
Iron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH) is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum. Illumina arrays containing over 47,000 probes were used to study global transcriptional changes. Quantitative RT-PCR (Q-RT-PCR) was used to validate the microarray results. In the liver, the expression of 151 genes was altered in Hfe(-/-) mice while dietary iron overload changed the expression of 218 genes. There were 173 and 108 differentially expressed genes in the duodenum of Hfe(-/-) mice and mice with dietary iron overload, respectively. There was 93.5% concordance between the results obtained by microarray analysis and Q-RT-PCR. Overexpression of genes for acute phase reactants in the liver and a strong induction of digestive enzyme genes in the duodenum were characteristic of the Hfe-deficient genotype. In contrast, dietary iron overload caused a more pronounced change of gene expression responsive to oxidative stress. In conclusion, Hfe deficiency caused a previously unrecognized increase in gene expression of hepatic acute phase proteins and duodenal digestive enzymes.
铁是一种必需的微量元素，其在十二指肠中的吸收通常受到严格调节。与 HFE 相关的遗传性血色素沉着症（HH）的特征是铁调节激素——hepcidin 的异常低表达，导致铁吸收增加。肝脏对于铁稳态至关重要，因为它是 hepcidin 的主要产生部位。本研究旨在探索和比较 Hfe 缺陷和饮食铁过载对小鼠肝脏和十二指肠全基因组转录组反应。使用包含超过 47000 个探针的 Illumina 阵列来研究全局转录变化。实时定量 RT-PCR（Q-RT-PCR）用于验证微阵列结果。在肝脏中，Hfe(-/-) 小鼠的 151 个基因表达发生改变，而饮食铁过载改变了 218 个基因的表达。Hfe(-/-) 小鼠和饮食铁过载的十二指肠中分别有 173 个和 108 个差异表达基因。微阵列分析和 Q-RT-PCR 结果之间的一致性为 93.5%。肝脏中急性期反应物基因的过度表达和十二指肠中消化酶基因的强烈诱导是 Hfe 缺陷基因型的特征。相比之下，饮食铁过载导致对氧化应激反应的基因表达发生更明显的变化。总之，Hfe 缺乏导致肝脏急性期蛋白和十二指肠消化酶基因的表达显著增加，这是以前未被认识到的。
