Liver hepcidin and stainable iron expression in biliary atresia.
Hepcidin is a proposed mammalian host defense peptide that was identified on the basis of its antimicrobial activity, but it was later shown to be a crucial regulator of iron homeostasis and a mediator of the anemia of chronic inflammation. Hepcidin and stainable iron expression in biliary atresia (BA) were investigated in this study. Fresh liver tissues were obtained from 10 patients in the early stage of BA when they underwent Kasai's procedure, 9 in the late stage of BA when they received liver transplantation and 5 controls receiving liver resection for benign lesions other than cholestasis or fibrosis. Real-time quantitative reverse-transcription PCR (QRT-PCR), immunohistochemical staining and ELISA were performed to gauge hepcidin mRNA and protein expression in liver and plasma. Archival liver specimens from patients in the early and late stages of BA were treated with Perls' acid ferrocyanide technique for hepatic stainable iron. The results demonstrated that liver hepcidin mRNA expression was 100-fold lower in late-stage BA than in the early stage by QRT-PCR. Significantly weaker liver hepcidin immunostaining and lower plasma hepcidin levels were found in late-stage BA than in the early stage. There was also significantly lower stainable iron in the liver of late-stage BA. The major site of stainable iron was in Kupffer cells. The results support a role for hepcidin as a key regulator of mammalian iron metabolism and chronic inflammation, whose expression correlates with the degree of stainable iron in BA.
Huang
Ying-Hsien
YH
Department of Pediatrics, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan 833, ROC.
Yu-Hsieh
Hui
H
Huang
Chao-Cheng
CC
Shin-Mu
Vincent Tseng
VT
Tai
Ming-Hong
MH
Chen
Chao-Long
CL
Chuang
Jiin-Haur
JH
D023181:Antimicrobial Cationic Peptides / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001656:Biliary Atresia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002675:Child, Preschool; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D064451:Hepcidins; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D018076:DNA, Complementary; C578702:HAMP protein, human; D064451:Hepcidins; D012333:RNA, Messenger; D007501:Iron