Study to establish the role of JAK2 and SMAD1/5/8 pathways in the inhibition of hepcidin by polysaccharides from Angelica sinensis

Current understanding of the molecular mechanisms involved in hepcidin (HAMP) suppression by ASP (schematic). The iron-regulated pathway and the inflammatory pathway are the two well-studied regulation pathways of hepcidin. In the iron-regulated pathway, the circulating amount of transferrin-bound iron binds to its two receptors (TfR1 and TfR2), which communicate with each other via iron-specific adaptor HFE and sensitize the BMP receptor to its ligands (e.g., BMP6). Membrane-linked co-receptor hemojuvelin (HJV) also potentiates activation of the BMP receptor, which then controls hepcidin transcription via SMAD1/5/8. Hepcidin transcription is increased appreciably by inflammation, predominantly through the activity of IL-6, its receptor, and its canonical JAK2-STAT3 pathway.295