Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver
Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver
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DOI：
10.1172/jci200524356
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发表时间：
2005-05-01
影响因子：
15.9
通讯作者：
Andrews, NC
中科院分区：
文献类型：
--
作者：
Gunshin, H;Fujiwara, Y;Andrews, NC
溶质载体家族11，成员2（SLC11A2）是已知参与细胞铁摄取的唯一跨膜铁转运蛋白。它被广泛表达，并被认为在肠铁吸收、红细胞铁利用、肝铁积累、胎盘铁转移和其它过程中起重要作用。以前的研究表明，其他转运蛋白可能存在，但其生理意义仍然不确定。为了确定Slc11a2在体内的活性，我们灭活了全局和选择性编码它的鼠基因。我们发现，胎儿Slc11a2是不需要母胎铁转移，但Slc11a2活性是必不可少的出生后肠道非血红素铁吸收。Slc11a2也是红细胞前体发育过程中正常血红蛋白产生所必需的。然而，肝细胞和大多数其他细胞必须有一个替代的，至今未知的，铁摄取机制。我们以前表明，Slc11a2作为血色素沉着症肠铁进入的主要门户网站。然而，小鼠Hfe的失活改善了缺乏Slc11a2的动物的表型。
Solute carrier family 11, member 2 (SLC11A2) is the only transmembrane iron transporter known to be involved in cellular iron uptake. it is widely expressed and has been postulated to play important roles in intestinal iron absorption, erythroid iron utilization, hepatic iron accumulation, placental iron transfer, and other processes. Previous studies have suggested that other transporters might exist, but their physiological significance remained uncertain. To define the activities of Slc11a2 in vivo, we inactivated the murine gene that encodes it globally and selectively. We found that fetal Slc11a2 is not needed for materno-fetal iron transfer but that Slc11a2 activity is essential for intestinal non-heme iron absorption after birth. Slc11a2 is also required for normal hemoglobin production during the development of erythroid precursors. However, hepatocytes and most other cells must have an alternative, as-yet-unknown, iron uptake mechanism. We previously showed that Slc11a2 serves as the primary portal for intestinal iron entry in hemochromatosis. However, inactivation of murine Hfe ameliorates the phenotype of animals lacking Slc11a2.