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Characterization of hepcidin response to holotransferrin in novel recombinant TfR1 HepG2 cells.
- Source :
-
Blood cells, molecules & diseases [Blood Cells Mol Dis] 2016 Oct; Vol. 61, pp. 37-45. Date of Electronic Publication: 2016 Jun 30. - Publication Year :
- 2016
-
Abstract
- Hepcidin is the key regulator of systemic iron homeostasis. The iron-sensing mechanisms and the role of intracellular iron in modulating hepatic hepcidin secretion are unclear. Therefore, we created a novel cell line, recombinant-TfR1 HepG2, expressing iron-response-element-independent TFRC mRNA to promote cellular iron-overload and examined the effect of excess holotransferrin (5g/L) on cell-surface TfR1, iron content, hepcidin secretion and mRNA expressions of TFRC, HAMP, SLC40A1, HFE and TFR2. Results showed that the recombinant cells exceeded levels of cell-surface TfR1 in wild-type cells under basal (2.8-fold; p<0.03) and holotransferrin-supplemented conditions for 24h and 48h (4.4- and 7.5-fold, respectively; p<0.01). Also, these cells showed higher intracellular iron content than wild-type cells under basal (3-fold; p<0.03) and holotransferrin-supplemented conditions (6.6-fold at 4h; p<0.01). However, hepcidin secretion was not higher than wild-type cells. Moreover, holotransferrin treatment to recombinant cells did not elevate HAMP responses compared to untreated or wild-type cells. In conclusion, increased intracellular iron content in recombinant cells did not increase hepcidin responses compared to wild-type cells, resembling hemochromatosis. Furthermore, TFR2 expression altered within 4h of treatment, while HFE expression altered later at 24h and 48h, suggesting that TFR2 may function prior to HFE in HAMP regulation.<br /> (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Antigens, CD drug effects
Antigens, CD genetics
Hemochromatosis Protein blood
Hemochromatosis Protein drug effects
Hep G2 Cells
Hepcidins drug effects
Humans
Iron blood
Iron Overload
RNA, Messenger blood
Receptors, Transferrin drug effects
Receptors, Transferrin genetics
Recombinant Proteins
Telomeric Repeat Binding Protein 2 blood
Telomeric Repeat Binding Protein 2 drug effects
Time Factors
Hepcidins blood
Transferrin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0961
- Volume :
- 61
- Database :
- MEDLINE
- Journal :
- Blood cells, molecules & diseases
- Publication Type :
- Academic Journal
- Accession number :
- 27667164
- Full Text :
- https://doi.org/10.1016/j.bcmd.2016.06.008