Stratum-specific expression of human transferrin receptor increases iron in mouse epidermis
Stratum-specific expression of human transferrin receptor increases iron in mouse epidermis
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DOI：
10.1038/sj.jid.5700127
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发表时间：
2006-03-01
影响因子：
6.5
通讯作者：
Shofner, Joshua
中科院分区：
文献类型：
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作者：
Milstone, Leonard M.;Adams, Brian D.;Shofner, Joshua
表皮脱落占人体每天铁损失的20%。然而，人们对表皮中铁含量的调节机制知之甚少。为了测试转铁蛋白受体在调节表皮铁含量中的重要性，我们创建了具有人转铁蛋白受体的层特异性表达的转基因小鼠。角蛋白 14 启动子主要将受体靶向基底、增殖的角质形成细胞；外皮蛋白 (Inv) 启动子将受体靶向基底上层、分化的角质形成细胞。表皮和毛发中的铁含量存在年龄和部位依赖性差异。在两种类型的转基因小鼠中，表皮铁含量随着年龄的增长而增加，并且在第 8 周时，与同窝对照小鼠相比，转基因小鼠的表皮铁含量增加了 2-3 倍。角蛋白 14-人转铁蛋白受体 (hTfR) 转基因毛发中的铁含量增加了 2 倍，Inv-hTfR 转基因毛发中的铁含量增加了 30%。在表皮铁含量增加的转基因动物中没有观察到总体或组织学变化。铁蛋白的表达在正常表皮中较低，但在两个转基因系中都大大增加，表明它可能是这些动物中额外铁的储存库。这些数据表明，控制转铁蛋白受体表达足以调节表皮中增殖或分化的角质形成细胞中的铁含量。
Epidermal desquamation accounts for 20% of the body's iron loss each day. Yet, little is known about how iron content in epidermis is regulated. To test the importance of the transferrin receptor in regulating iron content in epidermis, we created transgenic mice that have stratum-specific expression of the human transferrin receptor. The keratin 14 promoter targeted the receptor primarily to basal, proliferating keratinocytes; the involucrin ( Inv) promoter targeted the receptor to suprabasal, differentiating keratinocytes. There were age-and site-dependent differences in iron content in the epidermis and hair. In both types of transgenic mice, epidermal iron content increased with age and at 8 weeks was 2-3-fold greater in transgenic mice compared to littermate controls. Iron was increased up to 2-fold in hair of keratin 14-human transferrin receptor (hTfR) transgenics and 30% in Inv-hTfR transgenics. No gross or histological changes were seen in transgenic animals with increased iron in the epidermis. Ferritin expression, which was low in normal epidermis, was greatly increased in both transgenic lines, indicating that it is the likely depot for the extra iron in these animals. These data show that control of transferrin receptor expression is sufficient to regulate iron content in proliferating or differentiating keratinocytes in the epidermis.