The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation

The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation
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DOI:
10.1210/en.2006-1331
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发表时间:
2007-06-01
期刊:
影响因子:
4.8
通讯作者:
Kulaksiz, Hasan
Kulaksiz, Hasan
中科院分区:
医学2区
文献类型:
--
作者:
Merle, Uta;Fein, Evelyn;Kulaksiz, Hasan

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肽激素hepcidin在铁稳态中起核心作用。它主要在肝脏中表达,受铁、缺氧和炎症的调节。尽管已经证明铁在心脏疾病(包括铁超载心肌病、心肌缺血-再灌注损伤和动脉粥样硬化)中起着关键的病理生理作用,但对hepcidin在心脏中的可能表达和作用知之甚少。本研究对hepcidin在大鼠心脏中的表达及调控进行了分析。研究了hepcidin在大鼠心脏模型中mRNA和蛋白水平的基础表达,并比较了其在肝脏中的调节作用。免疫荧光显微镜分析细胞定位。单次注射松节油16 h后,心肌hepcidin mRNA升高2倍以上,肝脏hepcidin mRNA升高3倍以上。缺氧后,肝脏中hepcidin的表达降低。相反,缺氧导致hepcidin在心脏mRNA和蛋白水平上的表达明显上调,同时心肌间盘区hepcidin的免疫反应性明显增强。铁调节肽激素hepcidin在心脏中的调节表达的发现表明hepcidin可能在心脏疾病中起重要作用。
The peptide hormone hepcidin plays a central role in iron homeostasis. It is predominantly expressed in the liver and regulated by iron, hypoxia, and inflammation. Although it has been shown that iron plays a key pathophysiological role in cardiac diseases, including iron-overload cardiomyopathy, myocardial ischemia-reperfusion injury, and atherosclerosis, very little is known about the putative expression and the role of hepcidin in the heart. In the present study, expression and regulation of hepcidin in rat heart were analyzed. Basal cardiac expression of hepcidin was demonstrated on mRNA and protein level in vivo in a rat model and compared with its regulation in the liver. The cellular localization was analyzed by immunofluorescence microscopy. Sixteen hours after a single injection of turpentine, a more than 2-fold increase of cardiac hepcidin mRNA and a more than 3-fold increase of hepatic hepcidin mRNA was observed. In response to hypoxia, expression of hepcidin in the liver decreased. In contrast, hypoxia resulted in a strong up-regulation of hepcidin expression on mRNA and protein level in the heart, accompanied by an increased immunoreactivity of hepcidin pronounced at the myocardial intercalated disc area. The finding of a regulated expression of the iron-regulatory peptide hormone hepcidin in the heart suggests that hepcidin may have an important role in cardiac diseases.