BMP-6 MEDIATES IRON-INDUCED HEPCIDIN EXPRESSION IN VIVO VIA AN HFE-DEPENDENT MECHANISM

Abstract

Hepcidin is the key regulator of iron homeostasis acting as a negative regulator of intestinal iron absorption. Several proteins have recently been identified to act as upstream regulators of hepcidin expression, such as HFE and hemojuvelin (HJV). Although hepcidin is regulated by iron, the molecules involved in this regulation and whether HFE is involved in this regulation remain to be clarified. Therefore, the aim of this study was to investigate the molecules involved in hepcidin regulation by iron and the role played by HFE in this regulation in vivo. To induce iron loading, wild-type mice were injected with iron, and to investigate whether HFE is involved in hepcidin regulation by iron and BMP-Smad signalling pathway, HFE KO mice were also examined in the setting of iron loading. The obtained results showed that iron regulates the expression of BMP-6, for which HJV acts as a co-receptor, and also induces phosphorylation of SMADs 1/5/8 in the liver which in turn may regulate hepcidin gene expression in response to iron. Moreover, HFE seems to be involved in the regulation of downstream signalling of BMP-6 that regulates hepcidin expression in response to iron loading. In conclusion, the obtained results suggest that hepcidin regulation by iron is modulated by the BMP-6/Smad signalling pathway in vivo. Moreover, HFE seems to be involved in the regulation of downstream signalling of BMP-6 that regulates hepcidin expression in response to iron loading in vivo. ,