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背景
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Hepcidin, also known as Liver Expressed Antimicrobial Protein 1 (LEAP-1), is a peptide hormone that is involved in the regulation of iron metabolism. It is synthesized as a preprohormone that is cleaved intracellularly and secreted as a mature 25 amino acid peptide . Hepcidin contains eight cysteine residues that form four disulfide bonds which appear to be important for stability in biological fluids. It is predominantly expressed, processed, and secreted by hepatocytes. Hepcidin expression is positively regulated by inflammation via IL-6/JAK2/ STAT3 signaling, endoplasmic reticulum stress, and BMP-6. BMP-6-dependent Hepcidin induction involves RGM-C/Hemojuvelin, which acts as a co-receptor for BMP-6. Conversely, Hepcidin expression is negatively regulated by MMP?15/MT2?MMP and multiple erythropoietic stimuli, including anemia, hypoxia, and Erythropoietin. MMP-15 downregulates Hepcidin expression by interacting with and cleaving RGM-C. Hepcidin was originally identified in human blood and urine as an antimicrobial peptide. It has since been shown to regulate iron metabolism. Hepcidin binds the cellular iron exporter Ferroportin, and this interaction results in Ubiquitin-mediated degradation of both Hepcidin and Ferroportin. Degradation of Ferroportin results in reduced iron release from macrophages, hepatocytes, and duodenal enterocytes, suggesting that Hepcidin may be an effector of inflammatory hypoferremia.
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