《生命科学》 2012, 24(8): 753-756

Hemojuvelin在铁稳态平衡中的关键作用

陈文杰^1*，王福俤²

(1 哈佛大学医院麻省总医院系统生物学中心贫血信号研究所，波士顿，美国；2 中国科学院上海生命科学研究院营养科学研究所，上海 200031)

摘　要：
    

摘　要：铁调素(hepcidin) 是由肝脏分泌的一种肽类激素，它通过改变细胞膜上ferroportin 的水平而调节全身铁代谢。Ferroportin 是唯一已知的哺乳动物中的铁外排通道，它表达在小肠细胞的基底外侧膜和巨噬细胞的质膜上。铁调素结合ferroportin 导致其在溶酶体内降解，从而减少铁从饮食的吸收和巨噬细胞铁的释放。Hemojuvelin (HJV) 是一种glycosylphosphatidyl inositol (GPI) 相连的膜蛋白，它作为骨形态发生蛋白(BMP)的共受体可以激活肝细胞Smad 信号通路和铁调素表达。除了表达在细胞膜上，hemojuvelin 还可以被切割并分泌到胞外，形成可溶性蛋白。由furin 切割产生的可溶性HJV 可以选择性地结合到BMP 配体，抑制内源性BMP 诱导的铁调素表达。TMPRSS6 也被认为可以切割细胞膜上HJV 并影响铁调素的表达。最近的研究表明，HJV 还可能参与脂肪组织对铁代谢的调控。综述了近期对细胞膜HJV 和可溶性HJV 如何调节铁调素的表达与铁代谢的研究结果，并对这一研究领域需要填补的空白进行了初步探讨。
关键词：铁稳态；铁调素；Hemojuvelin
中图分类号： O614.81+1 文献标志码：A

    

收稿日期：2012-06-29
基金项目：国家重点基础研究发展计划(2009CB-941400， 2011CB966200， 2012BAD33B05)；国家自然科学基金项目(31030039， 10979071， 30970665)；上海市科委项目(10JC1416800)
*通信作者：E-mail: chen.wenjie@mgh.harvard.edu
的分子调控机制。

The critical role of Hemojuvelin in iron homeostasis

CHEN Wen-Jie^1*， WANG Fudi²

(1 Program in Anemia Signaling Research， Division of Nephrology， Program in Membrane Biology， Center for Systems Biology， Massachusetts General Hospital， Harvard Medical School， Boston， MA， USA; 2 Institute for Nutritional Sciences， Shanghai Institut

Abstract:


Abstract: Hepcidin， a peptide hormone secreted by the liver， regulates systemic iron metabolism by changing the levels of ferroportin on the cell membrane. Ferroportin， the only known mammalian cellular iron exporter， is expressed on the basolateral membrane of small intestinal enterocytes and the plasma membrane of macrophages. Hepcidin binding of ferroportin leads to internalization and degradation of ferroportin in lysosomes， which decreases iron absorption from the diet and iron release from macrophages that recycle iron from senescent erythrocytes. Hemojuvelin (HJV)， a glycosylphosphatidyl inositol (GPI) -linked membrane protein， acts as a bone morphogenetic protein (BMP) co-receptor to activate hepcidin expression through a SMAD signaling pathway in hepatocytes. In addition to residing on the cell membrane， hemojuvelin can be cleaved and secreted from cells in a soluble form. Soluble hemojuvelin， produced after cleavage by furin， can selectively bind to BMP ligands and inhibit endogenous and BMP-induced hepcidin expression. TMPRSS6 has been shown to cleave hemojuvelin on the cell membrane and affect hepcidin expression. Most recent studies suggest HJV may be involved in the regulation of iron metabolism by adipose tissue. This review summarizes the current understanding of the mechanism by which membrane HJV and soluble HJV regulate hepcidin expression and iron metabolism. We also discuss gaps in the knowledge that will need to be filled by future research.
Key words: iron metabolism; hepcidin; hemojuvelin