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. Author manuscript; available in PMC: 2021 Apr 1.
Published in final edited form as: Curr Opin Anaesthesiol. 2020 Apr;33(2):240–245. doi: 10.1097/ACO.0000000000000825

Fig. 1. Regulation of hepcidin (HAMP) transcription.

Fig. 1

Under high iron conditions or oxidative stress, BMP6 binds to BMP receptor (BMPR) which stimulates the phosphorylation of SMAD1,5,8. SMAD4 binds to phosphorylated SMAD1,5,8 and the complex enters the nucleus to stimulate hepcidin expression. The coreceptor hemojuvelin (HJV) facilitates the binding of BMP6 to BMPR. Neogenin (Neo), transferrin receptor 2 (TfR2) and HFE increase the signaling by the BMPR. Note that TfR2 is distinct from transferrin receptor 1 (TfR1); while both TfR1 and TfR2 bind to the iron transport protein transferrin (Tf), only Tf binding to TfFR2 stimulates hepcidin expression. Matriptase 2 (M2) negatively regulates the signaling by cleaving HJV, HFE, and multiple other substrates. Hepcidin transcription can also be upregulated by inflammation through stimulation of the IL6 receptor and phosphorylation of STAT3. STAT3 increases C/EBPδ–dependent upregulation of hepcidin transcription.