Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload
Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload
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DOI：
10.1016/j.jhep.2008.03.011
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发表时间：
2008-07-01
影响因子：
25.7
通讯作者：
Piperno, Alberto
中科院分区：
文献类型：
--
作者：
Barisani, Donatella;Pelucchi, Sara;Piperno, Alberto
背景/目的：许多肝脏铁负荷过高的患者没有可识别的突变，经常表现为代谢紊乱和肝脏脂肪变性。由于代谢紊乱型肝铁超载(DHIO)的病理生理机制尚不清楚，本研究的目的是评估在这些患者中铁相关分子表达的可能变化。方法：采用定量-聚合酶链式反应(QRT)检测无铁超载的NAFLD患者和HFE-血色沉着症、重型β-地中海贫血和DHIO患者的肝活检组织中铁相关基因的表达水平。结果：DHIO大鼠尿中铁转运蛋白和铁出口蛋白的表达均未见明显改变。按铁超载量归一化后的信使核糖核酸和尿海普西丁水平明显低于对照组，尽管没有血色素沉着症或β-地中海贫血组那么低。结论：DHIO患者体内编码铁摄取和外排相关蛋白的mRNAs表达水平存在适当的调节，而蛋白合成的调节异常。尿海普西汀的相对升高可以解释DHIO的铁表型(巨噬细胞铁滞留较多，转铁蛋白饱和度低/正常)。(C)2008年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: Many patients with hepatic iron overload do not have identifiable mutations and often present with metabolic disorders and hepatic steatosis. Since the pathophysiology of Dysmetabolic Hepatic Iron Overload (DHIO) is still obscure, the aim of this study was to evaluate, in these patients, possible alterations in iron-related molecule expression.Methods: Iron-related gene mRNA levels were determined by quantitative-PCR in liver biopsies of subjects with NAFLD without iron overload and patients with HFE-hemochromatosis, beta-thalassemia major and DHIO. Urinary hepcidin was measured by immunoblotting.Results: No alterations in mRNA expression of either iron transporters or exporters were found in DHIO. mRNA and urinary hepcidin levels normalized for the amount of iron overload showed a significantly lower ratio than in controls, although not as low as in hemochromatosis or beta-thalassemia. Differently from what observed in hemochromatosis, hepcidin mRNA did not correlate with urinary hepcidin.Conclusions: Patients with DHIO show appropriate regulation of mRNAs encoding proteins involved in iron uptake and efflux but dysregulation of hepcidin production. The relatively elevated urinary hepcidin can explain the iron phenotype in DHIO (more macrophage iron retention and low/normal transferrin saturation). (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.