title: Hepcidin expression in iron overload diseases is variably modulated by circulating factors.
abstract: Hepcidin is a regulatory hormone that plays a major role in controlling body iron homeostasis. Circulating factors (holotransferrin, cytokines, erythroid regulators) might variably contribute to hepcidin modulation in different pathological conditions. There are few studies analysing the relationship between hepcidin transcript and related protein expression profiles in humans. Our aims were: a. to measure hepcidin expression at either hepatic, serum and urinary level in three paradigmatic iron overload conditions (hemochromatosis, thalassemia and dysmetabolic iron overload syndrome) and in controls; b. to measure mRNA hepcidin expression in two different hepatic cell lines (HepG2 and Huh-7) exposed to patients and controls sera to assess whether circulating factors could influence hepcidin transcription in different pathological conditions. Our findings suggest that hepcidin assays reflect hepatic hepcidin production, but also indicate that correlation is not ideal, likely due to methodological limits and to several post-trascriptional events. In vitro study showed that THAL sera down-regulated, HFE-HH and C-NAFLD sera up-regulated hepcidin synthesis. HAMP mRNA expression in Huh-7 cells exposed to sera form C-Donors, HFE-HH and THAL reproduced, at lower level, the results observed in HepG2, suggesting the important but not critical role of HFE in hepcidin regulation.
authors.affiliation: Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ravasi
authors.forename: Sara
authors.initials: S
authors.lastname: Pelucchi
authors.forename: Paola
authors.initials: P
authors.lastname: Trombini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mariani
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
authors.forename: Giulia Litta
authors.initials: GL
authors.lastname: Modignani
authors.forename: Matteo
authors.initials: M
authors.lastname: Pozzi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nemeth
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.forename: Donatella
authors.initials: D
authors.lastname: Barisani
authors.forename: Alberto
authors.initials: A
authors.lastname: Piperno
mesh_terms: D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D001706:Biopsy; D016207:Cytokines / Q000097:blood / Q000652:urine; D005786:Gene Expression Regulation; D006432:Hemochromatosis / Q000097:blood / Q000652:urine; D000071020:Hemochromatosis Protein; D056945:Hep G2 Cells; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000097:blood / Q000473:pathology / Q000652:urine; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000652:urine; D017086:beta-Thalassemia / Q000097:blood / Q000652:urine
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012333:RNA, Messenger; D014168:Transferrin; C110714:holotransferrin; D007501:Iron