Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression.
Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression.
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DOI：
10.1016/j.cmet.2009.01.010
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发表时间：
2009-03
期刊：
影响因子：
29
通讯作者：
Enns CA
中科院分区：
文献类型：
--
作者：
Gao J;Chen J;Kramer M;Tsukamoto H;Zhang AS;Enns CA
让身体感知铁水平以维持铁稳态的机制尚不清楚。最常见的遗传性铁超载患者在遗传性血色病蛋白HFE中存在突变。他们有较低水平的hepcidin，比未受影响的人。铁调素是一种肝肽激素，负性调节铁从肠流入血液。我们报告了两个肝细胞系，WIF-B细胞和HepG 2细胞转染HFE，铁调素的表达响应铁载转铁蛋白。当内源性转铁蛋白受体2（TfR 2）被抑制或在缺乏功能性TfR 2或HFE的原代肝细胞中时，该反应被消除。此外，转铁蛋白处理的HepG 2细胞转染HFE嵌合体只含有α3和胞质结构域可以上调hepcidin的表达。由于HFE α3结构域与TfR 2相互作用，这些结果支持我们的发现，TfR 2/HFE复合物是由holo-Tf转录调控hepcidin所必需的。
The mechanisms that allow the body to sense iron levels in order to maintain iron homeostasis are unknown. Patients with the most common form of hereditary iron overload have mutations in the hereditary hemochromatosis protein, HFE. They have lower levels of hepcidin, than unaffected individuals. Hepcidin, a hepatic peptide hormone, negatively regulates iron efflux from the intestines into the blood. We report two hepatic cell lines, WIF-B cells and HepG2 cells transfected with HFE, where hepcidin expression responded to iron-loaded transferrin. The response was abolished when endogenous transferrin receptor 2 (TfR2) was suppressed or in primary hepatocytes lacking either functional TfR2 or HFE. Furthermore, transferrin-treated HepG2 cells transfected with HFE chimeras containing only the α3 and cytoplasmic domains could upregulate hepcidin expression. Since the HFE α3 domain interacts with TfR2, these results supported our finding that TfR2/HFE complex is required for transcriptional regulation of hepcidin by holo-Tf.
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WIF-B细胞：用于研究肝细胞极性的体外模型。
影响因子：
7.8
作者：
Ihrke, G;Neufeld, E B;Meads, T;Shanks, M R;Cassio, D;Laurent, M;Schroer, T A;Pagano, R E;Hubbard, A L
通讯作者：
Hubbard, A L
影响因子：
168.9
作者：
Bridle, KR;Frazer, DM;Ramm, GA
通讯作者：
Ramm, GA
影响因子：
20.3
作者：
Johnson, MB;Enns, CA
通讯作者：
Enns, CA
影响因子：
--
作者：
KIM, DS;AHN, SK;PARK, SD
通讯作者：
PARK, SD
影响因子：
4.8
作者：
Goswami, Tapasree;Andrews, Nancy C.
通讯作者：
Andrews, Nancy C.