Iron and liver fibrosis: Mechanistic and clinical aspects

Figure 2 Schematic of mechanistic cross-connection between the transforming growth factor beta pathway and bone morphogenetic protein signaling. Shared signalling components between transforming growth factor beta (TGF-β) (fibrosis-related) and bone morphogenetic protein (iron-related) pathways have been shown in hepatic stellate cells and hepatocytes. Previous study demonstrated TGF-β-induced hepcidin expression in human macrophages, while Chen et al[44] showed that this occurred through TGF-β-RII/RI in mouse and human hepatocytes via the non-canonical pathway involving small mothers against decapentaplegic protein-1/5/8 phosphorylation. ALK: Activin receptor-like kinase; BMPR: Bone morphogenetic protein receptor; HFE: High iron protein; HSC: Hepatic stellate cell; mHJV: Membrane-bound hemojuvelin protein; P: Phosphorylation; SMAD: Small mothers against decapentaplegic protein; TFR: Transferrin receptor; TGF-β-R: Transforming growth factor receptor.