Matriptase-2, A Novel Suppressor of Hepcidin

The study explored the role of matriptase-2, a serine protease encoded by the TMPRSS6 gene, in suppressing hepcidin, a key regulator of iron metabolism. Matriptase-2 was found to be crucial in conditions of high iron demand, such as iron deficiency and erythropoietic expansion, by inhibiting hepcidin and promoting iron release. The research highlighted that mutations in TMPRSS6, observed in iron-refractory iron-deficiency anemia (IRIDA) patients, impaired the ability of matriptase-2 to cleave hemojuvelin, a co-receptor in the bone morphogenetic protein (BMP) pathway, thus failing to suppress hepcidin. This led to iron deficiency anemia and hair loss, as seen in the Mask mouse model and Tmprss6 -/- mice. The findings suggested that the BMP pathway is a primary regulator of hepcidin, and the study provided insights into the molecular pathogenesis of IRIDA.