ER stress controls iron metabolism through induction of hepcidin. Science 2009 Aug 14;325(5942):877-80
Date
08/15/2009Pubmed ID
19679815Pubmed Central ID
PMC2923557DOI
10.1126/science.1176639Scopus ID
2-s2.0-68949220321 (requires institutional sign-in at Scopus site) 274 CitationsAbstract
Hepcidin is a peptide hormone that is secreted by the liver and controls body iron homeostasis. Hepcidin overproduction causes anemia of inflammation, whereas its deficiency leads to hemochromatosis. Inflammation and iron are known extracellular stimuli for hepcidin expression. We found that endoplasmic reticulum (ER) stress also induces hepcidin expression and causes hypoferremia and spleen iron sequestration in mice. CREBH (cyclic AMP response element-binding protein H), an ER stress-activated transcription factor, binds to and transactivates the hepcidin promoter. Hepcidin induction in response to exogenously administered toxins or accumulation of unfolded protein in the ER is defective in CREBH knockout mice, indicating a role for CREBH in ER stress-regulated hepcidin expression. The regulation of hepcidin by ER stress links the intracellular response involved in protein quality control to innate immunity and iron homeostasis.
Author List
Vecchi C, Montosi G, Zhang K, Lamberti I, Duncan SA, Kaufman RJ, Pietrangelo AMESH terms used to index this publication - Major topics in bold
3T3 CellsAnimals
Antimicrobial Cationic Peptides
Cell Line, Tumor
Cyclic AMP Response Element-Binding Protein
Endoplasmic Reticulum
Hepcidins
Homeostasis
Humans
Immunity, Innate
Iron
Liver
Mice
Mice, Knockout
Mutation
Promoter Regions, Genetic
Protein Folding
RNA Interference
Spleen
Stress, Physiological
Transcriptional Activation
