铁输出蛋白铁转运蛋白/溶质载体家族40成员1（Ferroportin/Slc40a1）对铁稳态至关重要。

The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.

作者信息

Donovan Adriana, Lima Christine A, Pinkus Jack L, Pinkus Geraldine S, Zon Leonard I, Robine Sylvie, Andrews Nancy C

机构信息

Children's Hospital Boston, Boston, Massachusetts 02115, USA.

出版信息

Cell Metab. 2005 Mar;1(3):191-200. doi: 10.1016/j.cmet.2005.01.003.

DOI:10.1016/j.cmet.2005.01.003

PMID:16054062

Abstract

Ferroportin (SLC40A1) is an iron transporter postulated to play roles in intestinal iron absorption and cellular iron release. Hepcidin, a regulatory peptide, binds to ferroportin and causes it to be internalized and degraded. If ferroportin is the major cellular iron exporter, ineffective hepcidin function could explain manifestations of human hemochromatosis disorders. To investigate this, we inactivated the murine ferroportin (Fpn) gene globally and selectively. Embryonic lethality of Fpn(null/null) animals indicated that ferroportin is essential early in development. Rescue of embryonic lethality through selective inactivation of ferroportin in the embryo proper suggested that ferroportin has an important function in the extraembryonic visceral endoderm. Ferroportin-deficient animals accumulated iron in enterocytes, macrophages, and hepatocytes, consistent with a key role for ferroportin in those cell types. Intestine-specific inactivation of ferroportin confirmed that it is critical for intestinal iron absorption. These observations define the major sites of ferroportin activity and give insight into hemochromatosis.

摘要

铁转运蛋白（SLC40A1）是一种铁转运体，推测其在肠道铁吸收和细胞铁释放过程中发挥作用。铁调素是一种调节肽，它与铁转运蛋白结合并使其内化和降解。如果铁转运蛋白是主要的细胞铁输出蛋白，那么铁调素功能异常可能解释人类血色素沉着症的症状表现。为了对此进行研究，我们在整体和选择性水平上使小鼠铁转运蛋白（Fpn）基因失活。Fpn（null/null）动物胚胎致死表明铁转运蛋白在发育早期至关重要。通过在胚胎本身选择性失活铁转运蛋白来挽救胚胎致死，这表明铁转运蛋白在胚外脏内胚层中具有重要功能。铁转运蛋白缺陷的动物在肠上皮细胞、巨噬细胞和肝细胞中积累铁，这与铁转运蛋白在这些细胞类型中的关键作用一致。肠道特异性失活铁转运蛋白证实了其对肠道铁吸收至关重要。这些观察结果确定了铁转运蛋白活性的主要位点，并为血色素沉着症提供了深入见解。