Arnold Jayantha, Sangwaiya Arvind, Bhatkal Bharati, Arnold Ahran
Department of Gastroenterology, Ealing Hospital NHS Trust, Uxbridge Road, Southall, Middlesex, UB1 3HW, United Kingdom.
Med Hypotheses. 2008;70(6):1197-200. doi: 10.1016/j.mehy.2007.10.007. Epub 2007 Dec 3.
Recent findings indicate a principal role for Hepcidin in iron homeostasis. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. Under normal conditions influx and efflux of iron from duodenal enterocytes is regulated by Ferroportin. Ferroportin is a Hepcidin binding protein expressed in duodenal enterocytes. Hepcidin is a peptide synthesised in the liver and is the main regulator of iron homeostasis. It is a defensin like protein and exhibits anti-microbial and anti-fungal activity. The Hepcidin gene is principally expressed in hepatocytes but to a lesser extent in neutrophils and macrophages. Hereditary Haemochromatosis is caused by disruption of iron homeostasis due to mutations in the HFE gene (C282Y or H63D). Unrestricted uptake of iron by duodenal enterocytes causes iron overload which is the hallmark of the disease. Current thinking is that defective Hepcidin synthesis or defective iron-sensing mechanisms leading to Hepcidin deficiency is the cause of iron overload in HFE-Haemochromatosis. Thus HFE-Haemochromatosis has been described as an endocrine disease. Basal levels of Hepcidin appear to be normal in HFE-Haemochromatosis patients. This contradicts current theories of defective Hepcidin synthesis as the cause of Hereditary HFE-Haemochromatosis. We propose that the defect in HFE-Haemochromatosis is the loss of Hepcidin surge in response to intake of dietary iron and is not as a result of reduced synthesis.
近期研究结果表明，铁调素在铁稳态中起主要作用。铁调素也被认为在炎症或慢性病患者贫血的发病机制中发挥重要作用。在正常情况下，十二指肠肠上皮细胞中铁的流入和流出由铁转运蛋白调节。铁转运蛋白是一种在十二指肠肠上皮细胞中表达的铁调素结合蛋白。铁调素是一种在肝脏中合成的肽，是铁稳态的主要调节因子。它是一种防御素样蛋白，具有抗菌和抗真菌活性。铁调素基因主要在肝细胞中表达，但在中性粒细胞和巨噬细胞中的表达程度较低。遗传性血色素沉着症是由HFE基因（C282Y或H63D）突变导致铁稳态破坏引起的。十二指肠肠上皮细胞不受限制地摄取铁会导致铁过载，这是该疾病的标志。目前的观点认为，铁调素合成缺陷或导致铁调素缺乏的铁感应机制缺陷是HFE型血色素沉着症中铁过载的原因。因此，HFE型血色素沉着症被描述为一种内分泌疾病。HFE型血色素沉着症患者的铁调素基础水平似乎正常。这与目前认为铁调素合成缺陷是遗传性HFE型血色素沉着症病因的理论相矛盾。我们提出，HFE型血色素沉着症的缺陷在于对膳食铁摄入的反应中铁调素激增的丧失，而不是合成减少的结果。
