Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood
Background Iron overload is one of common complications of β-thalassemia. Systemic iron homeostasis is regulated by iron-regulatory hormone, hepcidin, which inhibits intestinal iron absorption and iron recycling by reticuloendothelial system. In addition, body iron status and requirement can be alte...
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PeerJ Inc.
2020-03-01
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| author | Chanita Sanyear Punnee Butthep Wiraya Eamsaard Suthat Fucharoen Saovaros Svasti Patarabutr Masaratana |
| author_facet | Chanita Sanyear Punnee Butthep Wiraya Eamsaard Suthat Fucharoen Saovaros Svasti Patarabutr Masaratana |
| author_sort | Chanita Sanyear |
| collection | DOAJ |
| description | Background Iron overload is one of common complications of β-thalassemia. Systemic iron homeostasis is regulated by iron-regulatory hormone, hepcidin, which inhibits intestinal iron absorption and iron recycling by reticuloendothelial system. In addition, body iron status and requirement can be altered with age. In adolescence, iron requirement is increased due to blood volume expansion and growth spurt. Heterozygous β-globin knockout mice (Hbbth3/+; BKO) is a mouse model of thalassemia widely used to study iron homeostasis under this pathological condition. However, effects of age on iron homeostasis, particularly the expression of genes involved in hemoglobin metabolism as well as erythroid regulators in the spleen, during adolescence have not been explored in this mouse model. Methods Iron parameters as well as the mRNA expression of hepcidin and genes involved in iron transport and metabolism in wildtype (WT) and BKO mice during adolescence (6–7 weeks old) and adulthood (16–20 weeks old) were analyzed and compared by 2-way ANOVA. Results The transition of adolescence to adulthood was associated with reductions in duodenal iron transporter mRNA expression and serum iron levels of both WT and BKO mice. Erythrocyte parameters in BKO mice remained abnormal in both age groups despite persistent induction of genes involved in hemoglobin metabolism in the spleen and progressively increased extramedullary erythropiesis. In BKO mice, adulthood was associated with increased liver hepcidin and ferroportin mRNA expression along with splenic erythroferrone mRNA suppression compared to adolescence. Conclusion Our results demonstrate that iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood. The present study underscores the importance of the age of thalassemic mice in the study of molecular or pathophysiological changes under thalassemic condition. |
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| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:53:48Z |
| publishDate | 2020-03-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-07f1e3fe9d514b2da97b38ffd27a3f362023-12-03T10:13:46ZengPeerJ Inc.PeerJ2167-83592020-03-018e880210.7717/peerj.8802Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthoodChanita Sanyear0Punnee Butthep1Wiraya Eamsaard2Suthat Fucharoen3Saovaros Svasti4Patarabutr Masaratana5Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandThalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Bangkok, ThailandThalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Bangkok, ThailandDepartment of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandBackground Iron overload is one of common complications of β-thalassemia. Systemic iron homeostasis is regulated by iron-regulatory hormone, hepcidin, which inhibits intestinal iron absorption and iron recycling by reticuloendothelial system. In addition, body iron status and requirement can be altered with age. In adolescence, iron requirement is increased due to blood volume expansion and growth spurt. Heterozygous β-globin knockout mice (Hbbth3/+; BKO) is a mouse model of thalassemia widely used to study iron homeostasis under this pathological condition. However, effects of age on iron homeostasis, particularly the expression of genes involved in hemoglobin metabolism as well as erythroid regulators in the spleen, during adolescence have not been explored in this mouse model. Methods Iron parameters as well as the mRNA expression of hepcidin and genes involved in iron transport and metabolism in wildtype (WT) and BKO mice during adolescence (6–7 weeks old) and adulthood (16–20 weeks old) were analyzed and compared by 2-way ANOVA. Results The transition of adolescence to adulthood was associated with reductions in duodenal iron transporter mRNA expression and serum iron levels of both WT and BKO mice. Erythrocyte parameters in BKO mice remained abnormal in both age groups despite persistent induction of genes involved in hemoglobin metabolism in the spleen and progressively increased extramedullary erythropiesis. In BKO mice, adulthood was associated with increased liver hepcidin and ferroportin mRNA expression along with splenic erythroferrone mRNA suppression compared to adolescence. Conclusion Our results demonstrate that iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood. The present study underscores the importance of the age of thalassemic mice in the study of molecular or pathophysiological changes under thalassemic condition.https://peerj.com/articles/8802.pdfHeterozygous β-globin knockout miceHepcidinAgeThalassemiaIron transporters |
| spellingShingle | Chanita Sanyear Punnee Butthep Wiraya Eamsaard Suthat Fucharoen Saovaros Svasti Patarabutr Masaratana Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood PeerJ Heterozygous β-globin knockout mice Hepcidin Age Thalassemia Iron transporters |
| title | Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood |
| title_full | Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood |
| title_fullStr | Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood |
| title_full_unstemmed | Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood |
| title_short | Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood |
| title_sort | iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood |
| topic | Heterozygous β-globin knockout mice Hepcidin Age Thalassemia Iron transporters |
| url | https://peerj.com/articles/8802.pdf |
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