Ferroportin Is Essential for Iron Absorption During Suckling, But Is Hyporesponsive to the Regulatory Hormone Hepcidin
Ferroportin Is Essential for Iron Absorption During Suckling, But Is Hyporesponsive to the Regulatory Hormone Hepcidin
复制标题
DOI：
10.1016/j.jcmgh.2016.12.002
复制
发表时间：
2017-05-01
影响因子：
7.2
通讯作者：
Anderson, Gregory J.
中科院分区：
文献类型：
--
作者：
Frazer, David M.;Wilkins, Sarah J.;Anderson, Gregory J.
铁输出体膜铁转运蛋白对于乳鼠的高铁吸收是必不可少的，就像成年鼠一样。然而，与成人不同，铁的吸收是低反应的铁调节肽hepcidin在suckling.Background & AIMS：以前的研究表明，哺乳动物的铁吸收是难治性的刺激，通常会减少吸收成人。为了更好地了解哺乳期间铁吸收的调节，我们已经表征了铁调素，ferroportin，铁吸收之间的关系，在这个关键阶段的lifes.METHODS：为了确定ferroportin是否参与铁吸收在哺乳期间，吸收测定在特定的ferroportin基因敲除小鼠。还在哺乳跨膜丝氨酸蛋白酶6敲除小鼠中研究了组成性铁调素过表达对肠铁吸收的影响。最后，给乳鼠注射脂多糖以诱导铁调素表达。收集血液进行血清铁分析，并收集肝组织和十二指肠上皮细胞的基因和蛋白质的表达profiles.Results：铁吸收是非常低的哺乳ferroportin基因敲除小鼠，这表明ferroportin是负责大多数铁吸收在这个时候。然而，如在跨膜丝氨酸蛋白酶6敲除小鼠和注射脂多糖的小鼠中所见，哺乳期间铁调素的增加并不影响肠细胞膜铁转运蛋白水平。免疫荧光定位的ferroportin表明，该蛋白定位于十二指肠肠上皮细胞的基底外侧膜在哺乳和断奶mice.CONCLUSIONS：这些数据表明，高铁吸收发生在哺乳期间介导的ferroportin。然而，肠细胞膜铁转运蛋白是低反应的铁调素在这个时候，尽管表达的基底外侧膜。在哺乳期间阻止铁调素结合的膜铁转运蛋白的改变可以使铁吸收保持高水平，而不管铁调素表达水平如何，从而降低发育期间缺铁的可能性。
The iron exporter ferroportin is essential for the high iron absorption that occurs in suckling mice, as it is in adults. However, unlike adults, iron absorption is hyporesponsive to the inhibitory effect of the iron regulatory peptide hepcidin during suckling.BACKGROUND & AIMS: Previous studies have suggested that iron absorption in suckling mammals is refractory to stimuli that normally would decrease absorption in adults. To better understand the regulation of iron absorption during suckling, we have characterized the relationship between hepcidin, ferroportin, and iron absorption at this crucial stage of life.METHODS: To determine whether ferroportin is involved in iron absorption during suckling, absorption was measured in intestine-specific ferroportin knockout mice. The effect of constitutive hepcidin overexpression on intestinal iron absorption also was investigated in suckling transmembrane serine protease 6 knockout mice. Finally, suckling mice were injected with lipopolysaccharide to induce hepcidin expression. Blood was collected for serum iron analysis, and liver tissue and duodenal enterocytes were collected for gene and protein expression profiles.RESULTS: Iron absorption was very low in suckling ferroportin knockout mice, indicating that ferroportin is responsible for the majority of the iron absorbed at this time. However, increases in hepcidin during suckling, as seen in transmembrane serine protease 6 knockout mice and in mice injected with lipopolysaccharide, did not affect enterocyte ferroportin levels. Immunofluorescent localization of ferroportin showed that the protein localized to the basolateral membrane of duodenal enterocytes in both suckling and weaned mice.CONCLUSIONS: These data show that the high iron absorption occurring during suckling is mediated by ferroportin. However, enterocyte ferroportin is hyporesponsive to hepcidin at this time, despite being expressed on the basolateral membrane. Alterations to ferroportin that prevent hepcidin binding during suckling may allow iron absorption to remain high regardless of hepcidin expression levels, reducing the likelihood of iron deficiency during development.