What question did this study set out to answer?

The aim is to explore how the liver regulates iron and the implications for health and disease.

April 1, 2026Open Access

Iron sensing and regulatory mechanisms of the liver in health and disease

Key Points

The aim is to explore how the liver regulates iron and the implications for health and disease.
Examined hepcidin synthesis regulation via BMP/SMAD pathways.
Analyzed transferrin receptor 1 and Zip14 roles in iron uptake.
Investigated iron storage mechanisms involving ferritin and PCBPs.
Studied transcriptional regulation by HIF and NF-кB under varying iron levels.
Identified key pathways involved in hepcidin synthesis regulation.
Found that iron uptake mechanisms are vital for maintaining iron homeostasis.
Demonstrated dysregulation of iron regulatory mechanisms in hepatic diseases like HCC.

Abstract

The liver is the central organ for systemic iron metabolism, storing iron and producing the iron regulatory hormone, hepcidin. Hepcidin synthesis is regulated by endothelial cell-hepatocyte interaction via the bone morphogenic protein (BMP)/BMP receptor/hemojuvelin/SMAD pathways. Hepatocellular iron uptake from the circulation is mediated by transferrin receptor 1, for transferrin-bound iron, and Zip14, for non-on transferrin bound iron respectively. Within the cytosol, iron is shuttled by poly-r(C) binding proteins (PCBP) and is stored as ferritin. Regarding intracellular iron metabolism, iron responsive element (IRE)-iron responsive protein (IRP) interaction is essential for post-transcriptional regulation. In addition, iron-related proteins are transcriptionally regulated by hypoxia-inducible factor (HIF) and nuclear factor kappa B (NF-кB), depending on both iron and reactive oxygen species (ROS). In hepatic diseases, including hepatocellular carcinoma (HCC), these regulatory mechanisms are dysregulated.

Iron sensing and regulatory mechanisms of the liver in health and disease

Key Points

Abstract

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