Regulation of hepatic hepcidin expression by transferrin receptor-2

遗传性血色素沉着症（HH）是一种常见的遗传性疾病。铁超载会对肝脏、心脏和胰腺等特定器官造成损害，从而导致肝硬化、肝癌、糖尿病和心肌病。铁也会在关节中积聚，导致关节炎。肝脏是主要的铁感知器官，控制体内铁的稳态。转铁蛋白受体2 （TfR2）、HFE和血少年素（HJV）突变导致HH。据推测，TfR2可以感知体内的铁。TfR2在感应铁中的作用仍有争议。TfR2与HFE之间的关系仍存在争议。TfR2也与体外HJV相关。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，结合蛋白接近试验和磷蛋白组学分析，将用于确定体内TfR2的相互作用伙伴。这项研究的长期目标是了解扰乱体内铁平衡的关键蛋白质的突变如何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.