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.

ER stress controls iron metabolism through induction of hepcidin / Vecchi, Chiara; Montosi, Giuliana; K., Zhang; Lamberti, Igor; S. A., Duncan; R. J., Kaufman; Pietrangelo, Antonello. - In: SCIENCE. - ISSN 0036-8075. - STAMPA. - 325:5942(2009), pp. 877-880. [10.1126/science.1176639]

ER stress controls iron metabolism through induction of hepcidin.

VECCHI, Chiara;MONTOSI, Giuliana;LAMBERTI, Igor;PIETRANGELO, Antonello
2009

Abstract

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.
2009
325
5942
877
880
ER stress controls iron metabolism through induction of hepcidin / Vecchi, Chiara; Montosi, Giuliana; K., Zhang; Lamberti, Igor; S. A., Duncan; R. J., Kaufman; Pietrangelo, Antonello. - In: SCIENCE. - ISSN 0036-8075. - STAMPA. - 325:5942(2009), pp. 877-880. [10.1126/science.1176639]
Vecchi, Chiara; Montosi, Giuliana; K., Zhang; Lamberti, Igor; S. A., Duncan; R. J., Kaufman; Pietrangelo, Antonello
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/616675
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