1. Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies in Mask Mice.
- Author
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Krijt J, Frýdlová J, Gurieva I, Přikryl P, Báječný M, Steinbicker AU, Vokurka M, and Truksa J
- Subjects
- Animals, Bone Morphogenetic Protein 6 biosynthesis, Bone Morphogenetic Protein 6 genetics, Erythropoietin pharmacology, Female, GPI-Linked Proteins biosynthesis, GPI-Linked Proteins deficiency, GPI-Linked Proteins genetics, Gene Expression Regulation drug effects, Hemochromatosis Protein biosynthesis, Hemochromatosis Protein deficiency, Hemochromatosis Protein genetics, Hepcidins biosynthesis, Hepcidins genetics, Inhibitor of Differentiation Protein 1 biosynthesis, Inhibitor of Differentiation Protein 1 genetics, Iron Deficiencies, Iron, Dietary pharmacology, Liver metabolism, Male, Membrane Proteins deficiency, Membrane Proteins genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Organ Specificity, Promoter Regions, Genetic genetics, Protein Domains, Recombinant Proteins metabolism, Serine Endopeptidases deficiency, Serine Endopeptidases genetics, Spleen metabolism, GPI-Linked Proteins physiology, Hemochromatosis Protein physiology, Iron Overload metabolism, Membrane Proteins physiology, Serine Endopeptidases physiology
- Abstract
Matriptase-2, a serine protease expressed in hepatocytes, is a negative regulator of hepcidin expression. The purpose of the study was to investigate the interaction of matriptase-2 with hemojuvelin protein in vivo. Mice lacking the matriptase-2 proteolytic activity ( mask mice) display decreased content of hemojuvelin protein. Vice versa, the absence of hemojuvelin results in decreased liver content of matriptase-2, indicating that the two proteins interact. To further characterize the role of matriptase-2, we investigated iron metabolism in mask mice fed experimental diets. Administration of iron-enriched diet increased liver iron stores as well as hepcidin expression. Treatment of iron-overloaded mask mice with erythropoietin increased hemoglobin and hematocrit, indicating that the response to erythropoietin is intact in mask mice. Feeding of an iron-deficient diet to mask mice significantly increased spleen weight as well as the splenic content of erythroferrone and transferrin receptor proteins, indicating stress erythropoiesis. Liver hepcidin expression was decreased; expression of Id1 was not changed. Overall, the results suggest a complex interaction between matriptase-2 and hemojuvelin, and demonstrate that hepcidin can to some extent be regulated even in the absence of matriptase-2 proteolytic activity.
- Published
- 2021
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