title: BMPER protein is a negative regulator of hepcidin and is up-regulated in hypotransferrinemic mice.
abstract: The BMP/SMAD4 pathway has major effects on liver hepcidin levels. Bone morphogenetic protein-binding endothelial cell precursor-derived regulator (Bmper), a known regulator of BMP signaling, was found to be overexpressed at the mRNA and protein levels in liver of genetically hypotransferrinemic mice (Trf(hpx/hpx)). Soluble BMPER peptide inhibited BMP2- and BMP6-dependent hepcidin promoter activity in both HepG2 and HuH7 cells. These effects correlated with reduced cellular levels of pSMAD1/5/8. Addition of BMPER peptide to primary human hepatocytes abolished the BMP2-dependent increase in hepcidin mRNA, whereas injection of Bmper peptide into mice resulted in reduced liver hepcidin and increased serum iron levels. Thus Bmper may play an important role in suppressing hepcidin production in hypotransferrinemic mice.
authors.affiliation: Diabetes and Nutritional Sciences Division, School of Medicine, Kings College London, London WC2R 2LS, United Kingdom.
authors.forename: Neeta
authors.initials: N
authors.lastname: Patel
authors.forename: Patarabutr
authors.initials: P
authors.lastname: Masaratana
authors.forename: Javier
authors.initials: J
authors.lastname: Diaz-Castro
authors.forename: Gladys O
authors.initials: GO
authors.lastname: Latunde-Dada
authors.forename: Aakafa
authors.initials: A
authors.lastname: Qureshi
authors.forename: Pamela
authors.initials: P
authors.lastname: Lockyer
authors.forename: Molly
authors.initials: M
authors.lastname: Jacob
authors.forename: Matthew
authors.initials: M
authors.lastname: Arno
authors.forename: Pavle
authors.initials: P
authors.lastname: Matak
authors.forename: Ragai R
authors.initials: RR
authors.lastname: Mitry
authors.forename: Robin D
authors.initials: RD
authors.lastname: Hughes
authors.forename: Anil
authors.initials: A
authors.lastname: Dhawan
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McKie
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000235:genetics; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000494:pharmacology; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D023181:Antimicrobial Cationic Peptides; C525718:BMP2 protein, human; C476724:BMPER protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D002352:Carrier Proteins; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D010455:Peptides; D051785:Smad Proteins; D014168:Transferrin; C517553:crossveinless 2 protein, mouse; D007501:Iron