- 作者：Silvana Bonilla&dagger ; ; Joshua D. Prozialeck&dagger ; ; Padmini Malladi ; Xiaomin Pan ; Songtao Yu ; Hector Melin-Aldana ; Peter F. Whitington ; p-whitington@northwestern.edu
- 关键词：NH ; neonatal hemochromatosis phenotype ; GALD ; gestational alloimmune liver disease ; NTBI ; non-transferrin-bound iron ; TFR1 ; transferrin receptor-1 ; TFR2 ; transferrin receptor-2 ; DMT1 ; divalent metal transporter-1 ; ZIP14 ; solute carrier family 39 (zinc tra
- 刊名：Journal of Hepatology
- 出版年：2012
- 期刊代码：162_01688278
- 类别：med
- 出版时间：June, 2012
- 卷：56
- 期：6
- 页码：1351-1355
- 文件大小：848 K
Background & Aims
Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux. Under the resulting conditions of iron overload, the tissue pattern of extrahepatic siderosis is determined by the normal expression of proteins involved in the import of non-transferrin-bound iron and the export of cellular iron.Methods
Liver and extrahepatic tissues from infants with gestational alloimmune liver disease were examined and compared to normal age-appropriate tissues.
Results
Serum iron indices indicate iron overload and excess non-transferrin bound iron in gestational alloimmune liver disease. The diseased liver showed significantly reduced hepcidin, hemojuvulin, and transferrin gene expression compared to the normal fetal and neonatal liver. Those extrahepatic tissues that are typically involved in pathological siderosis in neonatal hemochromatosis, whether from normal or diseased newborns, consistently expressed solute carrier family 39 (zinc transporter), member 14 (ZIP14) for non-transferrin-bound iron uptake and expressed little ferroportin for iron export.
Conclusions
Excess non-transferrin-bound iron in gestational alloimmune liver disease may result from fetal liver injury that causes reduced synthesis of key iron regulatory and transport proteins. Whereas, the pattern of extrahepatic siderosis appears to be determined by the normal capacity of various tissues to import non-transferrin-bound iron and not export cellular iron.