Liver Hepcidin and Stainable Iron Expression in Biliary Atresia

Abstract

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. (Pediatr Res 59: 662-666, 2006)

Cholestasis downregulate hepcidin expression through inhibiting IL-6-induced phosphorylation of signal transducer and activator of transcription 3 signaling

“…The liver mean hepcidin mRNA expression was 420-fold less in PBC than in normal control (P ¼ 0.01) (Figure 1), which was consistent with our previous report 11 that hepcidin mRNA expression decreased significantly in cholestatic cirrhosis of BA than that in normal child control. Meanwhile, the liver hepcidin mRNA expressions of HBV, HCV and alcohol-induced non-cholestatic cirrhosis showed no significant difference from the normal control (P ¼ 0.12, 0.13 and 0.29 respectively).…”

“…In our previous study, hepatic expression of hepcidin decreased remarkably in the cirrhotic liver due to BA 11 However, in the study of Aoki et al 12 liver hepcidin mRNA correlates only with iron stores, but not inflammation and viral genotype in patients with chronic hepatitis C. In addition, Bergmann et al 13 also showed that levels of hepcidin mRNA did not differ between the controls and cirrhotic livers. On the contrary, a significant decrease in serum prohepcidin was observed in patients with liver cirrhosis compared with healthy individuals, which was most prominent in patients with hepatitis C virus and alcohol-related liver cirrhosis.…”

The effect of ursodeoxycholic acid on Messenger RNA hepcidin expression associated with liver fibrosis in perposed cholestasis jaundice

“…Obstructive jaundice (OJ) increases the risk of liver injury and sepsis, leading to increased mortality [6,7,[11][12][13][14][15][16][17].…”

“…The state of cholestasis in various previous studies in animals and humans raises the stress associated with the induction of inflammatory cytokines and IL-6 [6][7][8][9].…”

“…Hepcidin mRNA expression can be done through qRT-PCR, or ELISA assay of plasma hepcidin. Increased Plasma hepcidin is proven associated with progression of liver fibrosis and correlated with prognosis [10][11][12][13].…”