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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。
Hepcidin is a peptide hormone secreted by the liver that regulates whole body iron metabolism by altering the level of ferroportin on the cell membrane. Ferroportin is the only known iron efflux channel in mammalian cells that is expressed on the basolateral membrane of small intestine cells and the plasma membrane of macrophages. Hepcidin, in combination with ferroportin, causes its degradation in the lysosome thereby reducing the absorption of iron from the diet and the release of iron from macrophages. Hemojuvelin (HJV) is a membrane protein linked to glycosylphosphatidylinositol (GPI). As a co-receptor for bone morphogenetic protein (BMP), Hemojuvelin (HJV) activates hepatocyte Smad signaling pathway and hepcidin expression. In addition to its expression on the cell membrane, hemojuvelin can also be cleaved and secreted extracellularly to form soluble proteins. Soluble HJV produced by furin cleavage selectively binds to BMP ligands and inhibits endogenous BMP-induced hepcidin expression. TMPRSS6 is also thought to cleave HJV on the cell membrane and affect hepcidin expression. Recent studies have shown that HJV may also be involved in the regulation of iron metabolism in adipose tissue. The recent research on how HJV and soluble HJV regulate the expression of hepcidin and iron metabolism was reviewed. The gaps that need to be filled in this field were also discussed.