Intracellular Regulation Limits the Response of Intestinal Ferroportin to Iron Status in Suckling Rats.

Abstract

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. 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. 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.