BACH1 regulates erythrophagocytosis and iron-recycling in β-thalassemia
Issued Date
2023-03-01
Resource Type
ISSN
13569597
eISSN
13652443
Scopus ID
2-s2.0-85146190719
Pubmed ID
36565308
Journal Title
Genes to Cells
Volume
28
Issue
3
Start Page
211
End Page
225
Rights Holder(s)
SCOPUS
Bibliographic Citation
Genes to Cells Vol.28 No.3 (2023) , 211-225
Suggested Citation
Penglong T., Saensuwanna A., Pholngam N., Tansila N., Buncherd H., Srinoun K. BACH1 regulates erythrophagocytosis and iron-recycling in β-thalassemia. Genes to Cells Vol.28 No.3 (2023) , 211-225. 225. doi:10.1111/gtc.13004 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82750
Title
BACH1 regulates erythrophagocytosis and iron-recycling in β-thalassemia
Other Contributor(s)
Abstract
Macrophages play essential roles in erythrophagocytosis and iron recycling. β-thalassemia is characterized by a genetic defect in hemoglobin synthesis, which increases the rate of iron recycling. We previously showed that reduced expression of the BTB and CNC homolog 1 (BACH1) gene leads to increased phagocytosis of abnormal RBCs by activated monocytes. However, the mechanisms underlying this abnormal RBC clearance remained unclear. Herein, the spleen and bone marrow cells of β-thalassemic mice were examined for erythrophagocytosis CD markers and iron-recycling genes. Higher expression levels of CD47 and CD163 on RBCs and macrophages, respectively, were observed in β-thalassemic mice than in wild-type cells. The decreased expression of BACH1 caused an increase in Nrf2, Spic, Slc40a1, and HMOX1 expression in splenic red pulp macrophages of thalassemic mice. To investigate BACH1 regulation, a macrophage cell line was transfected with BACH1-siRNA. Decreased BACH1 expression caused an increase in CD163 expression; however, the expression levels were lower when the cells were cultured in media supplemented with β-thalassemia/HbE patient plasma. Additionally, the iron recycling-related genes SPIC, SLC40A1, and HMOX1 were significantly upregulated in BACH1-suppressed macrophages. Our findings provide insights into BACH1 regulation, which plays an important role in erythrophagocytosis and iron recycling in thalassemic macrophages.