Transferrin receptor 1 mRNA is downregulated in placenta of hepcidin transgenic embryos

• Published in: FEBS letters Vol. 574; no. 1; pp. 187 - 191
• Main Authors: Martin, Marie Elise, Nicolas, Gaël, Hetet, Gilles, Vaulont, Sophie, Grandchamp, Bernard, Beaumont, Carole
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 10.09.2004
• Subjects: Animals; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - physiology; Base Sequence; DNA Primers; Down-Regulation; Embryo, Mammalian - metabolism; Female; Gapdh, glyceraldehyde-3-phosphate dehydrogenase; Hepcidin; Hepcidins; IRE, iron responsive element; Iron; Iron - metabolism; Iron regulatory protein; IRP, iron regulatory protein; Male; Mice; Mice, Transgenic; p.c., post-coı̈tum; Placenta; Placenta - metabolism; Receptors, Transferrin - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; TfR1, transferrin receptor 1; Transcriptional regulation; Transferrin receptor; Iron regulatory protein; Gapdh, glyceraldehyde-3-phosphate dehydrogenase; Placenta; IRP, iron regulatory protein; Iron; TfR1, transferrin receptor 1; Transcriptional regulation; p.c., post-coı̈tum; Hepcidin; Transferrin receptor; IRE, iron responsive element
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.08.010

We have previously shown that hepcidin transgenic embryos are severely anemic and die around birth. Here, we report that embryonic hepcidin transgene expression decreases transferrin receptor 1 (TfR1) mRNA level in placenta, as shown by cDNA microarray analysis and quantitative RT-PCR, by a mechanism which is independent of placenta iron content and iron responsive element/iron regulatory protein (IRE/IRP) activity. On the contrary, iron injections into pregnant mothers result in increased placenta iron and ferritin content, and reduced IRE binding activity of IRP1 leading to decreased TfR1 mRNA level. Taken together, these results suggest that hepcidin action on placenta is mostly through transcriptional downregulation of the iron uptake machinery.