ISREC - Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland.
Cell Metab. 2010 Sep 8;12(3):273-82. doi: 10.1016/j.cmet.2010.08.003.
To maintain appropriate body iron levels, iron absorption by the proximal duodenum is thought to be controlled by hepcidin, a polypeptide secreted by hepatocytes in response to high serum iron. Hepcidin limits basolateral iron efflux from the duodenal epithelium by binding and downregulating the intestinal iron exporter ferroportin. Here, we found that mice with an intestinal ferritin H gene deletion show increased body iron stores and transferrin saturation. As expected for iron-loaded animals, the ferritin H-deleted mice showed induced liver hepcidin mRNA levels and reduced duodenal expression of DMT1 and DcytB mRNA. In spite of these feedback controls, intestinal ferroportin protein and (59)Fe absorption were increased more than 2-fold in the deleted mice. Our results demonstrate that hepcidin-mediated regulation alone is insufficient to restrict iron absorption and that intestinal ferritin H is also required to limit iron efflux from intestinal cells.
为了维持适当的体内铁水平，人们认为近端十二指肠的铁吸收受到肝细胞分泌的多肽——铁调素的控制，铁调素会结合并下调肠道铁输出蛋白 ferroportin，从而限制基底外侧的铁流出十二指肠上皮细胞。在这里，我们发现，肠铁蛋白 H 基因缺失的小鼠表现出体内铁储存和转铁蛋白饱和度增加。正如铁负荷动物所预期的那样，铁蛋白 H 缺失的小鼠表现出肝内铁调素 mRNA 水平升高和十二指肠 DMT1 和 DcytB mRNA 表达降低。尽管存在这些反馈控制，但缺失小鼠的肠道铁蛋白蛋白和（59）Fe 吸收增加了两倍以上。我们的结果表明，铁调素介导的调节本身不足以限制铁吸收，而且肠道铁蛋白 H 也需要限制铁从肠道细胞中流出。
