The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression

This dataset includes the source data files for the manuscript, “The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression” by Caroline A. Enns, Shall Jue, Bethel Demissu, and An-Sheng Zhang Neogenin (NEO1) is a ubiquitously expressed, multifunctional receptor that binds hemojuvelin (HJV); both proteins are essential components within hepatocytes for maintaining systemic iron homeostasis. Previous research established that the targeted ablation of hepatic Neo1 or Hjv in mice markedly reduces expression of the central iron-regulatory hormone, hepcidin. Reduction in hepcidin results in unrestricted iron absorption that leads to severe systemic iron overload. Hepatic hepcidin expression is primarily induced via the bone morphogenetic protein (BMP) signaling pathway, which requires a complex of plasma membrane proteins, including HJV acting as a BMP co-receptor. However, the precise mechanism by which NEO1 and HJV are orchestrated to robustly activate this pathway remains poorly understood. In this study, we systemically investigated the mechanisms by which hepatic Neo1 coordinates with Hjv to facilitate hepcidin induction using various knockout mouse models. Our data indicate that while Hjv is a more potent inducer of hepcidin than hepatic Neo1, the simultaneous ablation of both Neo1 and Hjv greatly reduces hepcidin expression. These results suggest that these two proteins form a crucial functional axis for controlling hepcidin levels. Further analysis revealed that approximately 84% of hepcidin expression relies on the synergistic association of Neo1 with Hjv. In comparison, Hjv retains a significantly compromised (~12%) ability to induce hepcidin independently of Neo1, while Neo1 possesses only a residual (~3%) independent induction capacity. Collectively, these data support a model in which hepatic Neo1 acts primarily as a molecular scaffold to facilitate assembly of the hepcidin-inducing signaling complex through Hjv.