Transferrin receptor 1 mRNA is downregulated in placenta of hepcidin transgenic embryos.
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.
Martin
Marie Elise
ME
INSERM U409, Faculté de Médecine X. Bichat, Institut Fédératif de Recherche 02, 16 rue Henri Huchard, 75018 Paris, France.
Nicolas
Gaël
G
Hetet
Gilles
G
Vaulont
Sophie
S
Grandchamp
Bernard
B
Beaumont
Carole
C
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D064451:Hepcidins; D007501:Iron / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010920:Placenta / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D011990:Receptors, Transferrin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D007501:Iron