Hepcidin and iron-related gene expression in subjects with Dysmetabolic Hepatic Iron Overload.
OBJECTIVE
Many patients with hepatic iron overload do not have identifiable mutations and often present with metabolic disorders and hepatic steatosis. Since the pathophysiology of Dysmetabolic Hepatic Iron Overload (DHIO) is still obscure, the aim of this study was to evaluate, in these patients, possible alterations in iron-related molecule expression.


METHODS
Iron-related gene mRNA levels were determined by quantitative-PCR in liver biopsies of subjects with NAFLD without iron overload and patients with HFE-hemochromatosis, beta-thalassemia major and DHIO. Urinary hepcidin was measured by immunoblotting.


RESULTS
No alterations in mRNA expression of either iron transporters or exporters were found in DHIO. mRNA and urinary hepcidin levels normalized for the amount of iron overload showed a significantly lower ratio than in controls, although not as low as in hemochromatosis or beta-thalassemia. Differently from what observed in hemochromatosis, hepcidin mRNA did not correlate with urinary hepcidin.


CONCLUSIONS
Patients with DHIO show appropriate regulation of mRNAs encoding proteins involved in iron uptake and efflux but dysregulation of hepcidin production. The relatively elevated urinary hepcidin can explain the iron phenotype in DHIO (more macrophage iron retention and low/normal transferrin saturation).
Barisani
Donatella
D
Department of Experimental Medicine, University of Milano-Bicocca, Via Cadore 48, Monza 20052, Milan, Italy. donatella.barisani@unimib.it
Pelucchi
Sara
S
Mariani
Raffaella
R
Galimberti
Stefania
S
Trombini
Paola
P
Fumagalli
Daniela
D
Meneveri
Raffaella
R
Nemeth
Elizabeta
E
Ganz
Tomas
T
Piperno
Alberto
A
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000652:urine; D001706:Biopsy; D027682:Cation Transport Proteins / Q000235:genetics; D002570:Ceruloplasmin / Q000235:genetics; D005260:Female; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics / Q000652:urine; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics* / Q000652:urine; D008107:Liver Diseases / Q000235:genetics* / Q000473:pathology / Q000652:urine; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D015703:Antigens, CD; D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D002570:Ceruloplasmin; D064451:Hepcidins; D007501:Iron; D008565:Membrane Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C068126:CD71 antigen; C578702:HAMP protein, human; C492164:HEPH protein, human