BMP6 treatment compensates for the molecular defect and ameliorates hemochromatosis in Hfe knockout mice.

ABSTRACT:

Background & aims

Abnormal hepcidin regulation is central to the pathogenesis of HFE hemochromatosis. Hepatic bone morphogenetic protein 6 (BMP6)-SMAD signaling is a main regulatory mechanism controlling hepcidin expression, and this pathway was recently shown to be impaired in Hfe knockout (Hfe(-/-)) mice. To more definitively determine whether HFE regulates hepcidin expression through an interaction with the BMP6-SMAD signaling pathway, we investigated whether hepatic Hfe overexpression activates the BMP6-SMAD pathway to induce hepcidin expression. We then investigated whether excess exogenous BMP6 administration overcomes the BMP6-SMAD signaling impairment and ameliorates hemochromatosis in Hfe(-/-) mice.

Methods

The BMP6-SMAD pathway and the effects of neutralizing BMP6

SUBMITTER: Corradini E 

PROVIDER: S-EPMC3295242 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature