The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.
The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.
复制标题
DOI：
10.3389/fphar.2014.00034
复制
发表时间：
2014
影响因子：
5.6
通讯作者：
Enns CA
中科院分区：
文献类型：
--
作者：
Worthen CA;Enns CA
要预防铁超载和贫血等疾病，需要对体内铁元素进行微调。被认为是铁传感器的转铁蛋白受体2 （TfR2）在肝脏中表达，该蛋白的突变导致铁超载疾病III型遗传性血色素沉着症（HH）。随着功能性TfR2的丧失，肝脏产生的肽激素hepcidin减少了约2倍，该激素负责负调节从饮食中摄取铁。hepcidin表达的减少导致铁在肝脏、心脏、关节和胰腺中的缓慢积累，并导致肝硬化、心脏病、关节炎和糖尿病。TfR2可以结合血流中的铁负载转铁蛋白（Tf），用Tf处理的肝细胞通过刺激骨形态发生蛋白（BMP）信号通路使hepcidin表达增加2倍。失去功能性TfR2或其结合伙伴，即原始HH蛋白，会导致这种转铁蛋白敏感性的丧失。虽然对TfR2的贩运和调控了解很多，但其通过bmp信号通路的转铁蛋白敏感性机制仍不清楚。
Fine-tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron sensor, transferrin receptor 2 (TfR2), is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH). With the loss of functional TfR2, the liver produces about 2-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin (Tf) in the bloodstream, and hepatocytes treated with Tf respond with a 2-fold increase in hepcidin expression through stimulation of the bone morphogenetic protein (BMP)-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.
登录
查看更多内容
影响因子：
4.8
作者：
Giannetti, AM;Björkman, PJ
通讯作者：
Björkman, PJ
影响因子：
4.8
作者：
Goswami, Tapasree;Andrews, Nancy C.
通讯作者：
Andrews, Nancy C.
影响因子：
4.8
作者：
Abboud, S;Haile, DJ
通讯作者：
Haile, DJ
DOI：
10.1073/pnas.040548097
发表时间：
2000-02-29
影响因子：
11.1
作者：
Fleming, RE;Migas, MC;Sly, WS
通讯作者：
Sly, WS
影响因子：
20.3
作者：
Carlson, H;Zhang, AS;Enns, CA
通讯作者：
Enns, CA