Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo
Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo
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DOI：
10.1182/blood-2010-06-289082
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发表时间：
2011-01-20
期刊：
影响因子：
20.3
通讯作者：
Arosio, Paolo
中科院分区：
文献类型：
--
作者：
Poli, Maura;Girelli, Domenico;Arosio, Paolo
铁调素是铁稳态的主要调节剂，其在肝脏中的表达受铁、炎症和红细胞生成活性的调节，其机制涉及骨形态发生蛋白（BMP）结合其受体和辅助受体。在这里，我们表明，外源性肝素强烈抑制hepcidin在肝HepG 2细胞的表达在药理学浓度，可能涉及骨形态发生蛋白6螯合和SMAD信号的阻断的机制。用药理学剂量的肝素治疗小鼠抑制肝铁调素mRNA表达和SMAD磷酸化，降低脾铁浓度，并增加血清铁。此外，我们观察到血清hepcidin在5例肝素治疗，以防止深静脉血栓形成，这是伴随着血清铁的增加和C-反应蛋白水平的降低强烈减少。这些数据表明，肝素在调节铁稳态中的作用尚未得到认识，并表明了治疗铁限制性缺铁性贫血的新方法。（血。2011; 117（3）：997-1004）
Hepcidin is a major regulator of iron homeostasis, and its expression in liver is regulated by iron, inflammation, and erythropoietic activity with mechanisms that involve bone morphogenetic proteins (BMPs) binding their receptors and coreceptors. Here we show that exogenous heparin strongly inhibited hepcidin expression in hepatic HepG2 cells at pharmacologic concentrations, with a mechanism that probably involves bone morphogenetic protein 6 sequestering and the blocking of SMAD signaling. Treatment of mice with pharmacologic doses of heparin inhibited liver hepcidin mRNA expression and SMAD phosphorylation, reduced spleen iron concentration, and increased serum iron. Moreover, we observed a strong reduction of serum hepcidin in 5 patients treated with heparin to prevent deep vein thrombosis, which was accompanied by an increase of serum iron and a reduction of C-reactive protein levels. The data show an unrecognized role for heparin in regulating iron homeostasis and indicate novel approaches to the treatment of iron-restricted iron deficiency anemia. (Blood. 2011; 117(3): 997-1004)