The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis
The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis
复制标题
DOI：
10.1016/j.cmet.2005.01.003
复制
发表时间：
2005-03-01
期刊：
影响因子：
29
通讯作者：
Andrews, NC
中科院分区：
文献类型：
--
作者：
Donovan, A;Lima, CA;Andrews, NC
铁蛋白（SLC40A1）是一种铁转运蛋白，该铁转运蛋白在肠道吸收和细胞释放中起着作用。肝素是一种调节性肽，与铁托蛋白结合，并导致其内部化和降解。如果铁托蛋白是主要的细胞铁出口剂，则无效的肝素功能可以解释人类血色素沉着症的表现。为了调查这一点，我们在全球且有选择地使鼠铁蛋白（FPN）基因失活。 FPN（Null/Null）动物的胚胎致死性表明，铁蛋白在发育的早期至关重要。通过在胚胎中选择性失活的肾上腺素通过选择性失活而挽救胚胎致死性，这表明铁托蛋白在胚外内脏内胚层中具有重要功能。缺乏铁皮素的动物在肠细胞，巨噬细胞和肝细胞中积累了铁，这与铁托蛋白在这些细胞类型中的关键作用一致。铁蛋白的肠特异性灭活证实，它对于肠道吸收至关重要。这些观察结果定义了铁蛋白活性的主要部位，并深入了解血色素沉着症。
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.