Intracellular Regulation Limits the Response of Intestinal Ferroportin to Iron Status in Suckling Rats.
Intracellular Regulation Limits the Response of Intestinal Ferroportin to Iron Status in Suckling Rats.
复制标题
DOI：
10.1002/mnfr.202300617
复制
发表时间：
2024-02
影响因子：
5.2
通讯作者：
Lili Qiu;Mengxiao Hu;Xiyu Qin;Rui Song;Yanan Sun;Xiaoyu Wang
中科院分区：
文献类型：
--
作者：
Lili Qiu;Mengxiao Hu;Xiyu Qin;Rui Song;Yanan Sun;Xiaoyu Wang
范围铁状态通过铁吸收调节，因为没有主动铁排泄。二价金属离子转运蛋白-1（DMT 1）和铁转运蛋白（FPN）是哺乳动物铁吸收的两个关键蛋白，但哺乳动物对它们的调控与成年动物不同。本研究旨在探讨铁转运蛋白在哺乳期不同铁营养条件下的调节作用。方法和结果本研究在不同铁条件下培养乳鼠。出乎意料的是，在不同的铁状态下检测到不变的FPN。由于FPN是哺乳动物唯一已知的铁输出者，因此未改变的FPN限制了哺乳期间输出到血液中的铁。因此，检测在转录、转录后和翻译后水平调节FPN的因子。结果表明，在低铁状态下，Fpn mRNA上调，而可沉默Fpn mRNA的microRNA-485（miR-485）上调，限制Fpn mRNA的翻译。此外，血清hepcidin和肝脏Hamp mRNA表达上调，但环指蛋白217（Rnf 217）mRNA在高铁状态下保持不变，导致FPN在成年后没有下调。结论转译调控限制了肠道FPN蛋白对铁缺乏的反应，Rnf 217不能有效介导高铁状态下FPN的降解，这为哺乳期维持铁稳态提供了参考。
SCOPE Iron status is regulated via iron absorption as there is no active iron excretion. Divalent metal-ion transporter-1 (DMT1) and ferroportin (FPN) are two key proteins vital for iron absorption, but the regulation of them in suckling mammals differs from that in adults. This study aims to explore regulation of iron transporters under different iron conditions during suckling. METHODS AND RESULTS This study developed suckling rats under different iron conditions. Unexpectedly, unchanged FPN at different iron status are detected. Since FPN is the only known iron exporter for mammals, unchanged FPN limits iron exported into blood during suckling. Thus, factors regulating FPN at transcriptional, post-transcriptional, and post-translational levels are detected. Results showed that Fpn mRNA is upregulated, while micro RNA-485(miR-485) which could silence Fpn mRNA is upregulated at low iron status limiting translation of Fpn mRNA. Besides, serum hepcidin and liver Hamp mRNA are upregulated, but ring finger protein 217( Rnf217) mRNA remained unchanged at high iron status leading to FPN not downregulated as adults. CONCLUSIONS Overall, this study indicates that translational regulation limits intestinal FPN protein response to iron deficiency and Rnf217 cannot effectively mediate the degradation of FPN at high iron status, which provides a reference for maintaining iron homeostasis during suckling.