Iron-induced expression of BMP6 in intestinal cells is the main regulator of hepatic hepcidin expression in vivo

Recent studies identified bone morphogenic protein 6 (BMP6) as key regulator of hepatic hepcidin expression and iron metabolism but the cellular source of BMP6 and the reason for its specific effect on hepatocytes are unknown. Methods and Results: BMP6-/- mice on a 129Sv/Ev background fed with normal diet develop severe hepatic iron accumulation and reduced hepcidin expression with increasing age. This phenotype could be triggered in younger mice by feeding iron-supplemented diets or parenteral application of iron-dextran. Both treatments induced a marked upregulation of BMP6 expression in the small intestine. E…