Hfe Actions in Kupffer Cells Are Dispensable for Hepatic and Systemic Iron Metabolism.
Paul KnoopDilay YilmazRossana PaganoniPeter Steele-PerkinsAndreas GruberBanu AkdoganHans ZischkaKerstin LeopoldMaja Vujić SpasićPublished in: International journal of molecular sciences (2023)
Mutations in the HFE / Hfe gene cause Hereditary Hemochromatosis (HH), a highly prevalent genetic disorder characterized by elevated iron deposition in multiple tissues. HFE acts in hepatocytes to control hepcidin expression, whereas HFE actions in myeloid cells are required for cell-autonomous and systemic iron regulation in aged mice. To address the role of HFE specifically in liver-resident macrophages, we generated mice with a selective Hfe deficiency in Kupffer cells ( Hfe Clec4fCre ). The analysis of the major iron parameters in this novel Hfe Clec4fCre mouse model led us to the conclusion that HFE actions in Kupffer cells are largely dispensable for cellular, hepatic and systemic iron homeostasis.
Keyphrases
- induced apoptosis
- cell cycle arrest
- mouse model
- stem cells
- type diabetes
- iron deficiency
- endoplasmic reticulum stress
- copy number
- acute myeloid leukemia
- poor prognosis
- signaling pathway
- gene expression
- adipose tissue
- insulin resistance
- transcription factor
- immune response
- oxidative stress
- single cell
- skeletal muscle
- patient safety