Mena Natalia P, Esparza Andrés L, Núñez Marco T
Biology Department and Cell Dynamics and Biotechnology Research Center, Faculty of Sciences, Universidad de Chile, Santiago.
Biol Res. 2006;39(1):191-3. doi: 10.4067/s0716-97602006000100022.
Hepcidin (Hepc) is a 25 amino acid cationic peptide with broad antibacterial and antifungal actions. A likely role for Hepc in iron metabolism was suggested by the observation that mice having disruption of the gene encoding the transcription factor USF2 failed to produce Hepc mRNA and developed spontaneous visceral iron overload. Lately, Hepc has been considered the "stores regulator," a putative factor that signals the iron content of the body to intestinal cells. In this work, we characterized the effect of Hepc produced by hepatoma cells on iron absorption by intestinal cells. To that end, human Hepc cDNA was cloned and overexpressed in HepG2 cells and conditioned media from Hepc-overexpressing cells was used to study the effects of Hepe on intestinal Caco-2 cells grown in bicameral inserts. The results indicate that Hepc released by HepG2 inhibited apical iron uptake by Caco-2 cells, probably by inhibiting the expression of the apical transporter DMT1. These results support a model in which Hepc released by the liver negatively regulates the expression of transporter DMT1 in the enterocyte.
铁调素（Hepc）是一种由25个氨基酸组成的阳离子肽，具有广泛的抗菌和抗真菌作用。编码转录因子USF2的基因被破坏的小鼠无法产生Hepc mRNA并出现自发性内脏铁过载，这一观察结果提示了Hepc在铁代谢中可能发挥的作用。最近，Hepc被认为是“储存调节因子”，是一种向肠道细胞传递体内铁含量信号的假定因子。在这项研究中，我们对肝癌细胞产生的Hepc对肠道细胞铁吸收的影响进行了表征。为此，我们克隆了人Hepc cDNA并在HepG2细胞中过表达，并用来自过表达Hepc细胞的条件培养基研究Hepc对在双室插入物中生长的肠道Caco-2细胞的影响。结果表明，HepG2释放的Hepc抑制了Caco-2细胞顶端的铁摄取，可能是通过抑制顶端转运蛋白DMT1的表达。这些结果支持了一种模型，即肝脏释放的Hepc对肠细胞中转运蛋白DMT1的表达具有负调节作用。
