The role of heparin, heparanase and heparan sulfates in hepcidin regulation.

Hepcidin is considered the major regulator of systemic iron homeostasis in human and mice, and its expression in the liver is mainly regulated at a transcriptional level. Central to its regulation are the bone morphogenetic proteins, particularly BMP6, that are heparin binding proteins. Heparin was found to inhibit hepcidin expression and BMP6 activity in hepatic cell lines and in mice, suggesting that endogenous heparan sulfates are involved in the pathway of hepcidin expression. This was confirmed by the study of cells and mice overexpressing heparanase, the enzyme that hydrolyzes heparan sulfates, and by cellular models with altered heparan sulfates. The evidences supporting the role of heparan sulfate in hepcidin expression are summarized in this chapter and open the way for new understanding in hepcidin expression and its control in pathological condition.