Regulation of hepatic hepcidin expression by transferrin receptor-2

遗传性血色沉着症是一种常见的遗传性疾病。铁负荷过多会导致特定器官的损害，包括肝脏、心脏和胰腺，导致肝硬变、肝癌、糖尿病和心肌病。铁也会积聚在关节中，导致关节炎。肝脏是铁敏感的主要器官，控制体内的铁稳态。转铁蛋白受体2(TfR2)、HFE和血凝素(HJV)突变可导致HH。TfR2被认为是感觉体内的铁。TfR2在感应铁的过程中所扮演的角色仍然存在争议。TfR2和HFE之间的联系仍有争议。在体外，TfR2也与HJV相关。我们建议确定TfR2控制体内铁稳态的机制。在基因治疗试验中使用的腺相关病毒载体，结合蛋白质邻近分析和磷酸蛋白质组分析，将被用来确定TfR2在体内的相互作用伙伴。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，揭示身体调节铁平衡的机制。

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.