Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis
Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis
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DOI：
10.1016/s0140-6736(03)12602-5
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发表时间：
2003-02-22
期刊：
影响因子：
168.9
通讯作者：
Ramm, GA
中科院分区：
文献类型：
--
作者：
Bridle, KR;Frazer, DM;Ramm, GA
背景遗传性血色病铁稳态失调的机制尚不清楚。然而，一些研究结果表明，铁调素（一种肝源性肽）与肠道铁吸收之间存在联系，表明该分子可能在肝脏铁过载中发挥作用。为了探讨这种可能的关联，我们研究了hepcidin（HAMP）和铁转运（IREG 1）的患者，在正常对照组，并在HFE基因敲除mice.Methods的基因的肝脏表达，我们提取总RNA从27例HFE相关的血色病，7移植供体（对照），和HFE基因敲除小鼠的肝组织。HAMP和IREG 1 mRNA浓度通过核糖核酸酶保护试验检测，并相对于管家基因GAPD表达。结果与对照组相比，未经治疗的患者HAMP表达显著降低（5.4倍，95%CI 3.3-7.5; p
Background The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice.Methods We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD.Findings There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p