Into the matrix: regulation of the iron regulatory hormone hepcidin by matriptase-2.
Matriptase-2 is a recently identified membrane-bound, cell-surface serine protease expressed primarily in liver. Mutations in matriptase-2 in mice and humans cause iron-deficiency anemia that responds poorly to iron therapy. The poor response results from an inability to decrease hepcidin production during iron deficiency. Cell culture studies reveal that matriptase-2 inhibits hepcidin induction by cleaving membrane hemojuvelin, a potent activator of hepcidin transcription. As a novel suppressor of hepcidin expression, matriptase-2 emerges as a possible candidate for therapeutic interventions aimed at treating disorders of iron metabolism.
Knutson
Mitchell D
MD
Food Science and Human Nutrition Department, University of Florida, Gainesville, Florida 32611, USA. mdknutson@ifas.ufl.edu
D018798:Anemia, Iron-Deficiency / Q000188:drug therapy / Q000235:genetics*; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000627:therapeutic use; D008565:Membrane Proteins / Q000502:physiology*; D009154:Mutation; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction; D017211:Treatment Failure
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C467801:matriptase 2