Characterization of hepcidin response to holotransferrin in novel recombinant TfR1 HepG2 cells

Journal article


Mehta, K, Busbridge, M, Renshaw, D, Evans, RW, Farnaud, S and Patel, VB (2016). Characterization of hepcidin response to holotransferrin in novel recombinant TfR1 HepG2 cells. Blood Cells, Molecules, and Diseases. 61, pp. 37-45.
AuthorsMehta, K, Busbridge, M, Renshaw, D, Evans, RW, Farnaud, S and Patel, VB
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 (5 g/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 24 h and 48 h (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 4 h; 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 4 h of treatment, while HFE expression altered later at 24 h and 48 h, suggesting that TFR2 may function prior to HFE in HAMP regulation.

Keywords1103 Clinical Sciences; Immunology
Year2016
JournalBlood Cells, Molecules, and Diseases
Journal citation61, pp. 37-45
PublisherElsevier
ISSN1079-9796
Digital Object Identifier (DOI)doi:10.1016/j.bcmd.2016.06.008
Publication dates
Print30 Jun 2016
Publication process dates
Deposited02 Oct 2018
Accepted28 Jun 2016
Accepted author manuscript
License
CC BY-NC-ND 4.0
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https://openresearch.lsbu.ac.uk/item/87376

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