title: Hepcidin, show some self-control! How the hormone of iron metabolism regulates its own expression.
abstract: Does the hormone of iron metabolism, hepcidin, exhibit 'self-control'? Hepcidin is a small, disulfide-rich peptide synthesized by the liver, which plays a keystone role in regulating systemic iron metabolism in mammals. Hepcidin acts by binding and triggering the lysosomal degradation of the cellular iron exporter ferroportin. Ultimately, decreased ferroportin leads to decreased plasma iron levels. Although various modulators of HAMP (the hepcidin antimicrobial peptide gene) expression are known, no auto-regulatory pathway has been described. In their paper published in the Biochemical Journal in April 2013, Pandur et al. identify an auto-regulatory pathway in which prohepcidin regulates HAMP expression. The authors observe that prohepcidin can bind to the inflammation-regulated STAT3 (signal transducer and activator of transcription 3)-binding site in the HAMP promoter to negatively regulate HAMP expression. Furthermore, the authors find that the prohepcidin-binding partner, α-1 antitrypsin, inhibits prohepcidin's ability to decrease HAMP activity. This is significant as α-1 antitrypsin, similar to hepcidin, is an acute-phase reactant that is up-regulated by inflammation. In conclusion, the discovery of a hepcidin auto-regulatory pathway, first, supports the emerging notion that hepcidin regulation is exquisitely fine-tuned through a process of combinatorial control; and secondly, suggests that hepcidin may play a hand in its own deregulation in diseases of iron metabolism that involve aberrant cytokine signalling (e.g. the anaemia of inflammation).
authors.affiliation: Department of Pathology and Bosch Institute, Molecular Pharmacology and Pathology Program, Blackburn Building, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Darius J R
authors.initials: DJ
authors.lastname: Lane
authors.forename: Michael L-H
authors.initials: ML
authors.lastname: Huang
authors.forename: Des R
authors.initials: DR
authors.lastname: Richardson
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D011498:Protein Precursors / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D011498:Protein Precursors