HEPCIDIN AND THE ANEMIA OF CHRONIC DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 具体的目的是评估腺瘤肿瘤负荷和贫血之间的关系，以表征正常对照，贫血患者和糖原累积病Ia型（GSDIa）患者的铁吸收和分布，并确定铁调素作为其他炎症性疾病患者慢性疾病贫血的介导剂的作用。 铁稳态和铁调素表达之间的关系将在正常和病理状态下进行研究，包括GSDIa，幼年型类风湿性关节炎和炎症性肠病。 由于在糖原累积病患者的肝腺瘤中已经证明了铁调素表达不当，因此将在该人群中进行直接观察性研究，以进一步研究这些病变与红细胞生成和铁状态指标之间的临床相关性。 将在所有受试者中研究铁的口服吸收，以确定铁调素与铁吸收之间的关系。 对于炎性疾病，将在疾病缓解和加重期间进行口服铁激发试验和铁调素的直接测量。 铁调素和炎症标志物之间的关系也将被调查。 通过这些研究，铁调素作为慢性疾病贫血介质的作用将得到阐明。 对慢性疾病贫血的病理生理学的进一步了解将为贫血和铁稳态紊乱的新治疗奠定基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims are to evaluate the relationship between adenoma tumor burden and anemia, to characterize iron absorption and distribution in normal controls, anemic patients, and patients with glycogen storage disease type Ia (GSDIa) and to determine the role of hepcidin as a mediator of the anemia of chronic disease in patients with other inflammatory conditions. The relationship between iron homeostasis and hepcidin expression will be studied in normal and pathologic states including GSDIa, juvenile rheumatoid arthritis, and inflammatory bowel disease. As inappropriate hepcidin expression has been demonstrated in hepatic adenomas in patients with glycogen storage disease, direct observational studies in this population will be performed to allow further clinical correlation between these lesions and indices of erythropoiesis and iron status. Oral absorption of iron will be investigated in all subjects to define the relationship between hepcidin and iron absorption. For the inflammatory disorders, the oral iron challenge tests and direct measurement of hepcidin will be performed during periods of disease remission and exacerbation. The relationship between hepcidin and inflammatory markers will also be investigated. Through these studies, the role of hepcidin as a mediator of anemia of chronic disease will be elucidated. Improved understanding of the pathophysiology of the anemia of chronic disease will lay the foundation for new treatments for anemia and disorders of iron homeostasis.