EXPRESSION OF THE INSULIN-LIKE GROWTH FACTOR-II MANNOSE-6-PHOSPHATE RECEPTOR IN MULTIPLE HUMAN TISSUES DURING FETAL LIFE AND EARLY INFANCY
EXPRESSION OF THE INSULIN-LIKE GROWTH FACTOR-II MANNOSE-6-PHOSPHATE RECEPTOR IN MULTIPLE HUMAN TISSUES DURING FETAL LIFE AND EARLY INFANCY
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DOI：
10.1210/jc.75.2.424
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发表时间：
1992-08-01
影响因子：
5.8
通讯作者：
KIESS, W
中科院分区：
文献类型：
--
作者：
FUNK, B;KESSLER, U;KIESS, W
胰岛素样生长因子-II/甘露糖-6-磷酸（IGF-II/M6 P）受体已在许多细胞和组织中检测到。在大鼠中，IGF-II/M6 P受体表达存在显著的发育调节，该受体在胎儿和新生儿组织中含量高，此后下降。我们系统地研究了人IGF-II/M6 P受体蛋白在10个人胎儿和婴儿（孕23周至出生后24个月）组织中的表达。我们已经询问了1）不同器官之间是否存在差异表达，以及2）人类IGF-II/M6 P受体是否在妊娠23周至出生后24个月期间受到发育调控。使用含有2%十二烷基硫酸钠和2%Triton X-100的缓冲液从人体组织中提取蛋白质。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和使用抗IGF-II/M6 P受体抗血清（编号66416）和I-125-蛋白A或免疫过氧化物酶染色的免疫印迹法分析蛋白提取物的等分试样。在研究的所有组织中均检测到IGF-II/M6 P受体免疫反应性，心脏、胸腺和肾脏中表达的受体量最高，脑和肌肉中测得的受体含量最低。卵巢、睾丸、肺和脾的受体含量居中。IGF-II/M6 P受体的表观分子量（220，000千克，无二硫键还原）在不同组织中不同：脑中的受体分子量低于其他器官。免疫定量实验采用I-125-蛋白A和蛋白质提取物从人的肾脏在不同的年龄揭示了一个小的，虽然不显着，胎儿和出生后组织之间的受体含量的差异：在其他物种中，更大量的受体似乎是存在于胎儿比出生后的器官。此外，没有显着差异的受体含量之间的人胎肝和出生后早期的肝脏采用I-125-蛋白A-免疫定量测定在3个胎儿和5个出生后的肝脏组织样本。IGF结合蛋白（IGEBP）种类的分布，另一个丰富的和主要类别的IGF结合原则，也测量了人胎儿和出生后早期的肺，肝，肾，肌肉和脑中使用蛋白质配体印迹与I-125-IGF-II：与IGF-II/M6 P受体免疫反应性有不同类别的IGFBPs在不同的器官中的差异表达。总之，1）IGF-II/M6 P受体存在于多种人体组织中，2）人IGF-II/M6 P受体在不同器官中不同程度地表达，3）人中IGF-II/M6 P受体表达的发育调节程度比已经报道的大鼠或绵羊低得多，4）IGF-II/M6 P受体和IGFBPs在整个胎儿和出生后早期人类生命中的各种器官中的不同分布模式表明IGF结合原则在发育和生长中的重要和组织特异性作用。
The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF-II/M6P receptor antiserum (no. 66416) and I-125-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing I-125-protein A and protein extracts from human kidney at different ages revealed a small albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing I-125-protein A-immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with I-125-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs. In conclusion, 1) the IGF-II/M6P receptor is present in multiple human tissues, 2) the human IGF-II/M6P receptor is variably expressed in different organs, 3) there is a much lesser degree of developmental regulation of IGF-II/M6P receptor expression in the human than has been reported for the rat or sheep, 4) the differential pattern of distribution of IGF-II/M6P receptor and IGFBPs in the various organs throughout fetal and early postnatal human life points to an important and tissue specific role of the IGF binding principles in development and growth.