PUBLICATION
Hrg1 promotes heme-iron recycling during hemolysis in the zebrafish kidney
- Authors
- Zhang, J., Chambers, I., Yun, S., Phillips, J., Krause, M., Hamza, I.
- ID
- ZDB-PUB-180925-9
- Date
- 2018
- Source
- PLoS Genetics 14: e1007665 (Journal)
- Registered Authors
- Hamza, Iqbal
- Keywords
- none
- Datasets
- GEO:GSE109978
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cytophagocytosis/physiology*
- Erythrocytes/physiology*
- Female
- Gene Knockout Techniques
- Head Kidney/metabolism*
- Hematopoiesis/physiology
- Heme/metabolism
- Hemeproteins/genetics
- Hemeproteins/metabolism*
- Iron/metabolism
- Macrophages/metabolism
- Male
- Models, Animal
- Solute Carrier Proteins/genetics
- Solute Carrier Proteins/physiology*
- Zebrafish/physiology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- PubMed
- 30248094 Full text @ PLoS Genet.
Citation
Zhang, J., Chambers, I., Yun, S., Phillips, J., Krause, M., Hamza, I. (2018) Hrg1 promotes heme-iron recycling during hemolysis in the zebrafish kidney. PLoS Genetics. 14:e1007665.
Abstract
Heme-iron recycling from senescent red blood cells (erythrophagocytosis) accounts for the majority of total body iron in humans. Studies in cultured cells have ascribed a role for HRG1/SLC48A1 in heme-iron transport but the in vivo function of this heme transporter is unclear. Here we present genetic evidence in a zebrafish model that Hrg1 is essential for macrophage-mediated heme-iron recycling during erythrophagocytosis in the kidney. Furthermore, we show that zebrafish Hrg1a and its paralog Hrg1b are functional heme transporters, and genetic ablation of both transporters in double knockout (DKO) animals shows lower iron accumulation concomitant with higher amounts of heme sequestered in kidney macrophages. RNA-seq analyses of DKO kidney revealed large-scale perturbation in genes related to heme, iron metabolism and immune functions. Taken together, our results establish the kidney as the major organ for erythrophagocytosis and identify Hrg1 as an important regulator of heme-iron recycling by macrophages in the adult zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping