Prohepcidin localises to the Golgi compartment and secretory pathway in hepatocytes

Background/Aims: Hepcidin is a liver-expressed peptide which plays an important role in the regulation of iron metabolism. It is a negative regulator of iron absorption and release of iron from cells. The aims of this study were to analyse the expression and localisation of prohepcidin in liver and cell lines. Methods: We generated antibodies against recombinant mouse prohepcidin and studied its expression in cell lines, primary hepatocytes and livers of normal mice and mice with abnormalities in iron metabolism. Results: Prohepcidin localised to the secretory pathway, primarily the Golgi apparatus in liver cells and tissues. Hfe and β2-microglobulin knockout mice have similar levels of prohepcidin protein expression as compared to wild-type mice despite increased iron stores. Sex-linked anaemia mice have iron deficiency and no prohepcidin expression in the liver. Conclusions: Prohepcidin protein is present in the secretory pathway of liver cells. Despite iron loading, mouse models of haemochromatosis have comparatively normal levels of prohepcidin expression whereas mice with iron deficiency have no prohepcidin expression.