Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum.
Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum.
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DOI：
10.1073/pnas.96.4.1579
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发表时间：
1999-02
影响因子：
11.1
通讯作者：
A. Waheed;S. Parkkila;J. Saarnio;R. Fleming;Xiao Yan Zhou;S. Tomatsu;R. Britton;B. Bacon;W. Sly
中科院分区：
文献类型：
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作者：
A. Waheed;S. Parkkila;J. Saarnio;R. Fleming;Xiao Yan Zhou;S. Tomatsu;R. Britton;B. Bacon;W. Sly
在遗传性血色病（HH）中，肠道对膳食铁的吸收增加，导致组织中过量的铁积累并导致器官损伤。HH中有缺陷的HFE蛋白通常在十二指肠的隐窝肠上皮细胞中表达，在那里它具有独特的、主要是细胞内的定位。在胎盘中，HFE蛋白与转铁蛋白受体（TfR）共定位并形成稳定的结合，提供了HFE蛋白和铁转运之间的联系。在本研究中，我们研究了HFE蛋白的人十二指肠肠上皮细胞的TfR的关系，并测定了铁转铁蛋白结合铁和离子铁的摄取分离的隐窝和绒毛肠上皮细胞。免疫细胞化学结果显示，HFE蛋白和TfR均在肠腺上皮细胞中表达。Western印迹显示，与人胎盘中的情况一样，隐窝肠上皮细胞中的HFE蛋白与TfR和β 2-微球蛋白物理相关。隐窝细胞组分表现出显着更高的转铁蛋白结合铁的吸收比绒毛细胞。绒毛细胞对铁离子的吸收是腺细胞的2-3倍。我们建议，HFE蛋白质调节的隐窝肠上皮细胞从血浆中的转铁蛋白结合铁的摄取，并参与隐窝肠上皮细胞感知体内铁储备水平的机制。HH中的HFE基因突变引起的这种功能的损害可以在隐窝肠细胞中提供矛盾的信号，该信号编程分化中的肠细胞在它们成熟为绒毛肠细胞时吸收更多的膳食铁。
In hereditary hemochromatosis (HH), intestinal absorption of dietary iron is increased, leading to excessive iron accumulation in tissues and resultant organ damage. The HFE protein, which is defective in HH, normally is expressed in crypt enterocytes of the duodenum where it has a unique, predominantly intracellular localization. In placenta, the HFE protein colocalizes with and forms a stable association with the transferrin receptor (TfR), providing a link between the HFE protein and iron transport. In the present study, we examined the relationship of the HFE protein to the TfR in enterocytes of the human duodenum and measured the uptake of transferrin-bound iron and ionic iron by isolated crypt and villus enterocytes. Immunocytochemistry showed that the HFE protein and TfR both are expressed in the crypt enterocytes. Western blots showed that, as was the case in human placenta, the HFE protein in crypt enterocytes is physically associated with the TfR and with beta2-microglobulin. The crypt cell fraction exhibited dramatically higher transferrin-bound iron uptake than villus cells. On the other hand, the villus cells showed 2-3 times higher uptake of ionic iron than crypt cells. We propose that the HFE protein modulates the uptake of transferrin-bound iron from plasma by crypt enterocytes and participates in the mechanism by which the crypt enterocytes sense the level of body iron stores. Impairment of this function caused by HFE gene mutations in HH could provide a paradoxical signal in crypt enterocytes that programs the differentiating enterocytes to absorb more dietary iron when they mature into villus enterocytes.