De Domenico Ivana, Ward Diane M, Kaplan Jerry
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84106, USA.
J Clin Invest. 2007 Jul;117(7):1755-8. doi: 10.1172/JCI32701.
Hepcidin is a peptide hormone secreted by the liver that plays a central role in the regulation of iron homeostasis. Increased hepcidin levels result in anemia while decreased expression is the causative feature in most primary iron overload diseases. Mutations in hemochromatosis type 2 (HFE2), which encodes the protein hemojuvelin (HJV), result in the absence of hepcidin and an early-onset form of iron overload disease. HJV is a bone morphogenetic protein (BMP) coreceptor and HJV mutants have impaired BMP signaling. In this issue of the JCI, Babitt and colleagues show that BMPs are autocrine hormones that induce hepcidin expression (see the related article beginning on page 1933). Administration of a recombinant, soluble form of HJV decreased hepcidin expression and increased serum iron levels by mobilizing iron from splenic stores. These results demonstrate that recombinant HJV may be a useful therapeutic agent for treatment of the anemia of chronic disease, a disorder resulting from high levels of hepcidin expression.
铁调素是一种由肝脏分泌的肽类激素，在铁稳态调节中起核心作用。铁调素水平升高会导致贫血，而表达降低是大多数原发性铁过载疾病的致病特征。编码血色素沉着蛋白（HJV）的2型血色素沉着症（HFE2）发生突变，会导致铁调素缺乏以及早发型铁过载疾病。HJV是一种骨形态发生蛋白（BMP）共受体，HJV突变体会损害BMP信号传导。在本期《临床研究杂志》中，巴比特及其同事表明，BMP是诱导铁调素表达的自分泌激素（见第1933页开始的相关文章）。给予重组可溶性HJV可通过动员脾脏储存的铁来降低铁调素表达并提高血清铁水平。这些结果表明，重组HJV可能是治疗慢性病贫血（一种因铁调素高表达导致的疾病）的有用治疗剂。
