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. Author manuscript; available in PMC: 2011 Aug 21.
Published in final edited form as: Annu Rev Nutr. 2010 Aug 21;30:105–122. doi: 10.1146/annurev.nutr.012809.104804

Figure 1. Regulators of hepcidin synthesis during inflammation.

Figure 1

Activation of STAT1/3 by cytokine signaling promotes transcription through a STAT element. IL-6 plays a predominant role in this inflammatory response. This element appears to be regulated through the nearby BMP-RE1 via SMAD activation, which is required for full promoter activity. A distal BMP-RE2 site is thought interact with the SMAD/STAT complex that brings distal and proximal regions of the hepcidin promoter into physical contact. SMAD signaling is activated through the HJV/BMP pathway. HJV is negatively regulated by matripase-2 cleavage; BMP signaling is negatively regulated by GDF15 and TWSG1. HFE interacts with TfR1 and may be released upon binding of diferric Tf. While binding of both diferric Tf and HFE to the TfR2 are known to stimulate hepcidin synthesis, the molecular aspects of this pathway remain unknown. In addition, ER stress response pathways involved in inflammation are known to induce hepcidin through at least two mechanisms: 1) negative regulation of C/EBPα by CHOP and 2) activation of CREBH, possibly in conjunction with activated (spliced) XBP-1.