Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis.
Hepatic hemosiderosis and increased iron absorption are common findings in cirrhosis. It has been proposed that a positive relation exists between intestinal iron absorption and the development of hepatic hemosiderosis. The current study investigated the duodenal expression of the iron transport molecules divalent metal transporter 1 (DMT1 [IRE]), iron-regulated gene 1 (Ireg1 [ferroportin]), hephaestin, and duodenal cytochrome b (Dyctb) in 46 patients with cirrhosis and 20 control subjects. Total RNA samples were extracted from duodenal biopsy samples and the expression of the iron transport genes was assessed by ribonuclease protection assays. Expression of DMT1 and Ireg1 was increased 1.5 to 3-fold in subjects with cirrhosis compared with iron-replete control subjects. The presence of cirrhosis per se and serum ferritin (SF) concentration were independent factors that influenced the expression of DMT1. However, only SF concentration was independently associated with Ireg1 expression. In cirrhosis, the expression of DMT1 and Ireg1 was not related to the severity of liver disease or cirrhosis type. There was no correlation between the duodenal expression of DMT1 and Ireg1 and the degree of hepatic siderosis. In conclusion, the presence of cirrhosis is an independent factor associated with increased expression of DMT1 but not Ireg1. The mechanism by which cirrhosis mediates this change in DMT1 expression has yet to be determined. Increased expression of DMT1 may play an important role in the pathogenesis of cirrhosis-associated hepatic iron overload.
Stuart
Katherine Anne
KA
Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia. Drkastuart@AOL.com
Anderson
Gregory Jon
GJ
Frazer
David Michael
DM
Murphy
Therese Luna
TL
Powell
Lawrie William
LW
Fletcher
Linda Maria
LM
Crawford
Darrell Henry
DH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D027682:Cation Transport Proteins / Q000235:genetics*; D045303:Cytochromes b / Q000235:genetics; D004386:Duodenum / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000453:epidemiology / Q000503:physiopathology; D033862:Iron-Binding Proteins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D012307:Risk Factors; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D045303:Cytochromes b; D007501:Iron; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C492164:HEPH protein, human