Iron deficiency anemia in inflammatory bowel disease

Figure 3 Signaling pathways regulating hepcidin expression in the liver. Enterocyte iron induces BMP6 expression. BMP6 is released via the portal vein to act on cell-surface receptors in the liver, BMPR-I, BMPR-II, and HJV, a co-receptor of BMP, leading to phosphorylation of cytosolic transcription factors, SMAD 1/5/8, which complex with SMAD 4[16,21]. This heteromeric complex translocates to the nucleus and enhances transcription of hepcidin gene, HAMP. In iron deficiency, HJV is cleaved by matriptase-2 activation reducing BMP signaling, and BMP is sequestered by s-HJV, preventing its interaction with plasma membrane HJV, decreasing hepcidin expression[21]. IL-6: Interleukin 6; BMP: Bone morphogenetic protein; HJV: Hemojuvelin; s-HJV: Soluble HJV; TfR2: Transferrin receptor 2; HFE: Hereditary hemochromatosis protein; BMPR: Bone morphogenetic protein receptors.