Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, MA 02114, USA.
Biochem Biophys Res Commun. 2013 Nov 15;441(2):383-6. doi: 10.1016/j.bbrc.2013.10.065. Epub 2013 Oct 21.
Hepcidin is a peptide hormone that is secreted by the liver and that functions as the central regulator of systemic iron metabolism in mammals. Its expression is regulated at the transcriptional level by changes in iron status and iron requirements, and by inflammatory cues. There is considerable interest in understanding the mechanisms that influence hepcidin expression because dysregulation of hepcidin production is associated with a number of disease states and can lead to iron overload or iron-restricted anemia. In order to shed light on the factors that alter hepcidin expression, we carried out experiments with HepG2 and HuH7, human hepatoma cell lines that are widely used for this purpose. We found that the addition of heat-inactivated fetal calf serum to these cells resulted in a significant dose- and time-dependent up-regulation of hepcidin expression. Serum also activated signaling events known to be downstream of bone morphogenetic proteins (BMPs), a group of molecules that have been implicated previously in hepcidin regulation. Inhibition of these signals with dorsomorphin significantly suppressed serum-induced hepcidin up-regulation. Our results indicate that a BMP or BMP-like molecule present in serum may play an important role in regulating hepcidin expression.
亚铁调素是一种由肝脏分泌的肽类激素，作为哺乳动物系统铁代谢的中枢调节剂。其表达在转录水平上受到铁状态和铁需求变化以及炎症信号的调节。人们对理解影响亚铁调素表达的机制非常感兴趣，因为亚铁调素产生的失调与许多疾病状态有关，并可能导致铁过载或缺铁性贫血。为了阐明改变亚铁调素表达的因素，我们用人肝癌细胞系 HepG2 和 HuH7 进行了实验，这些细胞系被广泛用于该目的。我们发现，向这些细胞中添加热失活胎牛血清会导致亚铁调素表达显著的剂量和时间依赖性上调。血清还激活了已知是骨形态发生蛋白（BMPs）下游的信号事件，BMPs 是一组先前被认为与亚铁调素调节有关的分子。用 Dorsomorphin 抑制这些信号显著抑制了血清诱导的亚铁调素上调。我们的结果表明，血清中存在的 BMP 或类似 BMP 的分子可能在调节亚铁调素表达中发挥重要作用。
