Pumping iron in the kidney
| Autor: | Jodie L. Babitt, Allison L. Fisher |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Iron Overload Ferroportin Kidney hemochromatosis iron Hepcidin Internal medicine medicine Homeostasis Humans Receptor ferroportin chemistry.chemical_classification biology renal tubules Chemistry Iron levels medicine.anatomical_structure Endocrinology Basic Research Nephrology biology.protein hepcidin Essential nutrient Hormone |
| Zdroj: | Kidney International |
| ISSN: | 1523-1755 |
| Popis: | The hepcidin/ferroportin axis controls systemic iron homeostasis by regulating iron acquisition from the duodenum and reticuloendothelial system, respective sites of iron absorption and recycling. Ferroportin is also abundant in the kidney, where it has been implicated in tubular iron reabsorption. However, it remains unknown whether endogenous hepcidin regulates ferroportin-mediated iron reabsorption under physiological conditions, and whether such regulation is important for kidney and/or systemic iron homeostasis. To address these questions, we generated a novel mouse model with an inducible kidney-tubule specific knock-in of fpnC326Y, which encodes a hepcidin-resistant ferroportin termed FPNC326Y. Under conditions of normal iron availability, female mice harboring this allele had consistently decreased kidney iron but only transiently increased systemic iron indices. Under conditions of excess iron availability, male and female mice harboring this allele had milder kidney iron overload, but greater systemic iron overload relative to controls. Additionally, despite comparable systemic iron overload, kidney iron overload occurred in wild type mice fed an iron-loaded diet but not in hemochromatosis mice harboring a ubiquitous knock-in of fpnC326Y. Thus, our study demonstrates that endogenous hepcidin controls ferroportin-mediated tubular iron reabsorption under physiological conditions. It also shows that such control is important for both kidney and systemic iron homeostasis in the context of iron overload. Graphical abstract |
| Databáze: | OpenAIRE |
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