The role of Matriptase-2 during the early postnatal development in humans

Hepcidin is the hepatic peptide hormone, which regulates the systemic iron homeostasis by degrading the only cellular iron exporter ferroportin. The transmembrane serine protease matriptase-2 (MT-2, encoded by TMPRSS6) is a major hepcidin inhibitor and mutations in TMPRSS6 gene are responsible of inherited iron refractory iron deficiency anemia (IRIDA), characterized by hypochromic microcytic anemia, low transferrin saturation and inappropriate normal/high levels of hepcidin. In this study we retrospectively analyzed the hematological parameters in the (neo) perinatal period of IRIDA patients to understand the role of matriptase-2 at birth and during early development. We found that anemia is not present at birth and thus we inferred that it is absent also in utero but develops after the second month of life. Our results might have implications to better understand iron homeostasis during early development in IRIDA patients and indicate that Mt2 is dispensable during fetal and neonatal life in humans, consistent with the idea that the downregulation of hepcidin by Mt2 becomes effective only with the introduction of dietary iron.