Regulation of hepatic hepcidin expression by transferrin receptor-2

遗传性血色病是一种常见的遗传性疾病。铁超负荷导致对特定器官的损害，包括肝脏、心脏和胰腺，导致肝硬化、肝癌、糖尿病、心肌病。铁也积累在关节引起关节炎。肝脏是主要的铁敏感器官，控制着体内铁的稳态。转铁蛋白受体2（TfR2）、HFE和血幼素（HJV）的突变导致HH。TfR2被假设为感知体内的铁。TfR2在感知铁中的作用仍然存在争议。TfR2和HFE之间的关系仍有争议。TfR2在体外也与HJV结合。我们建议确定TfR2控制体内铁稳态的机制。基因治疗试验中使用的腺相关病毒载体与蛋白质邻近测定和磷酸蛋白质组学分析组合将用于确定TfR2在体内的相互作用伴侣。这项研究的长期目标是了解干扰体内铁平衡的关键蛋白质的突变，揭示身体调节铁稳态的机制。

Hereditary hemochromatosis (HH) is a common inherited disorder. Iron overload results in damage to specific organs including the liver, heart, and pancreas resulting in cirrhosis of the liver, liver cancer, diabetes, cardiomyopathy. Iron also accumulates in joints causing arthritis. The liver is the major iron-sensing organ and controls iron homeostasis in the body. Mutations in transferrin receptor 2 (TfR2), HFE and hemojuvelin (HJV) lead to HH. TfR2 is hypothesized to sense iron in the body. The role that TfR2 plays in sensing iron remains controversial. The association between TfR2 and HFE is still debated. TfR2 also associates with HJV in vitro. We propose to determine the mechanisms by which TfR2 controls iron homeostasis in the body. Adeno- associated viral vectors used in gene therapy trials in combination with protein proximity assays and phosphoproteomic analysis will be utilized to determine the interaction partners of TfR2 in vivo. The long-term goal of this research is to understand how mutations in key proteins that disturb the iron balance in the body, reveal the mechanisms by which the body regulates iron-homeostasis.