Ontogenic changes in lactoferrin receptor and DMT1 in mouse small intestine: implications for iron absorption during early life.
Ontogenic changes in lactoferrin receptor and DMT1 in mouse small intestine: implications for iron absorption during early life.
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DOI：
10.1139/o06-059
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发表时间：
2006-06
期刊：
影响因子：
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通讯作者：
V. López;Yasushi A. Suzuki;B. Lönnerdal
中科院分区：
文献类型：
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作者：
V. López;Yasushi A. Suzuki;B. Lönnerdal
乳铁蛋白受体(LFR)可能参与生命早期肠道铁的转运。然而，已知的铁稳态是由二价金属转运蛋白1(DMT1；Nramp2/DCT1)在成人小肠中调节的。为了解释LFR在生命早期可能作为铁的替代运输途径的假设，我们使用免疫组织化学(IHC)检测了小鼠LFR(MLfR)和DMT1的定位。除研究LFR和DMT1在顶膜上的定位和丰度外，在出生后3周(出生后0、5、10和20天)分离肠刷状缘膜泡(BBMV)。我们发现mLfR在孕13.5天、15.5天和18.5天的胎鼠体内都有表达。在全肠匀浆中，pD0至pD20处检测到一条34kD的mLfR条带。免疫组化显示，DMT1蛋白在PD 0和PD 5有极少量表达，而PD 10主要定位于成熟肠的顶膜。BBMV分级显示DMT1的蛋白条带为50-120kD。在这些BBMV标本中，DMT1的顶膜相关的120kD条带随着年龄的增加而增加。然而，在相应的总匀浆中，只鉴定出脱糖形式的DMT1(50kD)。这些结果表明，DMT1在妊娠晚期是错误定位的，在生命早期表达最低，直到20岁时主要以脱糖形式表达。mLfR的免疫定位和丰富的蛋白表达表明，从LF获得的铁可能是该年龄段的主要铁摄取途径。总之，我们的发现支持这样一种观点，即在肠道中诱导依赖发育的DMT1表达之前，mLfR可能是一种替代的铁摄取途径。
It has been proposed that lactoferrin receptor (LfR) may be involved in intestinal iron transport during early life. However, it is known that iron homeostasis is regulated by divalent metal transporter 1 (DMT1; Nramp2/DCT1) in the adult small intestine. To address the hypothesis that LfR may play a role as an alternative iron transport pathway during early life, we used immunohistochemistry (IHC) to examine the localization of mouse LfR (mLfR) and DMT1. In addition to studying the localization and abundance of LfR and DMT1 on the apical membrane, intestinal brush-border membrane vesicles (BBMV) were isolated during the first 3 postnatal weeks (postnatal day (PD) 0, 5, 10, and 20). We found that mLfR is expressed in fetal mice as early as gestational days (GD) 13.5, 15.5, and 18.5. A 34 kD band for mLfR was detected at PD 0 through PD 20 in total intestine homogenate. However, mLfR protein did not appear in the BBMV preparations until PD 5 and was highly expressed at PD 10. By IHC, DMT1 protein was minimally observed at PD 0 and PD 5, but by PD 10 DMT1 was predominantly localized in the apical membrane of the maturing intestine. BBMV fractionation revealed 50-120 kD protein bands for DMT1. In these BBMV preparations, the apical-membrane-associated 120 kD band for DMT1 increased in abundance with age. However, in the corresponding total homogenates, only the deglycosylated form of DMT1 (50 kD) was identified. These results indicate that DMT1 is mislocalized during late gestation, minimally expressed during early life, and predominantly expressed in its deglycosylated form until PD 20. The immunolocalization and abundant protein expression of mLfR suggest that accrual of iron from Lf may be the principal iron uptake pathway at this age. In conclusion, our findings support the notion that until the development-dependent expression of DMT1 in the intestine is induced, mLfR may serve as an alternative iron uptake pathway.