From the Guidelines
The protein involved in hepatic sensing that regulates hepcidin is primarily hemojuvelin (HJV), along with other key proteins including bone morphogenetic protein 6 (BMP6), transferrin receptor 2 (TfR2), and human hemochromatosis protein (HFE). These proteins work together in the liver to sense iron levels in the body and adjust hepcidin production accordingly. When iron levels are high, this signaling pathway activates, increasing hepcidin production, which then reduces iron absorption from the gut and iron release from macrophages. Conversely, when iron levels are low, this pathway is suppressed, decreasing hepcidin and allowing more iron to enter circulation. This regulation is critical for maintaining proper iron homeostasis in the body. Disruptions in this sensing mechanism, particularly mutations in HFE, HJV, or TfR2, can lead to hereditary hemochromatosis, characterized by excessive iron absorption and potential organ damage. The BMP-SMAD signaling pathway is the primary mechanism through which these proteins regulate hepcidin transcription in response to iron status, as described in the study by 1.
Some key points to consider:
- HJV, BMP6, TfR2, and HFE are essential for regulating hepcidin production in response to iron levels 1.
- The BMP-SMAD signaling pathway plays a crucial role in hepcidin regulation, with BMP2 and BMP6 being the primary ligands involved 1.
- Hepcidin production is also influenced by inflammation, erythropoietic drive, and other factors, which can impact iron homeostasis 1.
- Mutations in HFE, HJV, or TfR2 can lead to hereditary hemochromatosis, highlighting the importance of these proteins in maintaining proper iron regulation 1.
Overall, the regulation of hepcidin by HJV, BMP6, TfR2, and HFE is critical for maintaining iron homeostasis, and disruptions in this pathway can have significant consequences for morbidity, mortality, and quality of life.
From the Research
Protein Involved in Hepatic Sensing and Regulation of Hepcidin
- Hemojuvelin (HJV) is a membrane protein that plays a crucial role in iron absorption and release from cells, and has anti-inflammatory properties 2, 3.
- HJV is highly expressed in the liver, skeletal muscle, and heart, and acts as a bone morphogenetic protein (BMP) co-receptor to regulate hepcidin expression via the SMAD pathway 2, 3.
- Mutations in the HJV gene can lead to juvenile hemochromatosis, a rare autosomal recessive disorder characterized by systemic iron overload and hepcidin deficiency 3, 4.
- HJV is essential for the regulation of hepcidin expression in response to iron stores, and its dysfunction can lead to iron overload or deficiency 5, 6.
- The BMP-SMAD pathway is a major positive driver of hepcidin expression in response to increased circulating iron or iron loading in organs 5.