REGULATION OF THE INSULIN-LIKE GROWTH-FACTOR SYSTEM DURING NORMAL RAT LUNG DEVELOPMENT
REGULATION OF THE INSULIN-LIKE GROWTH-FACTOR SYSTEM DURING NORMAL RAT LUNG DEVELOPMENT
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DOI：
10.1165/ajrcmb.12.1.7529031
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发表时间：
1995-01-01
影响因子：
6.4
通讯作者：
STILES, AD
中科院分区：
文献类型：
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作者：
MOATSSTAATS, BM;PRICE, WA;STILES, AD
胰岛素样生长因子(IGF)-I和IGF-II是一种小肽生长因子，它们与一种特定的膜受体I型IGF受体相互作用，刺激细胞增殖和/或分化。这些生长因子的作用及其对其受体的可用性受特定结合蛋白IGF结合蛋白(IGFBP)-1至-6的调节，IGFBP-1至-6与IGFS和IGF受体一起形成IGF系统。我们分析了从胎鼠(孕16天[E16]到孕22天[E22])和成年(60天龄)大鼠肺中提取的RNA，以了解IGF系统的每个组成部分的表达。IGF-I和-II RNA在整个胎儿发育过程中都有表达。胎儿和成人肺中IGF-I mRNA相对稳定，而IGF-II RNA在妊娠后期下降，低于Northern分析在成人肺中检测到的水平。I型IGF受体的表达在所研究的所有年龄中变化不大，而2型IGF受体RNA表现出发育调节，随着年龄的增长表达下降。在胎儿和成人肺中均未检测到IGFBP-1转录本。IGFBP-2RNA在胚胎16~22天表达，但其丰度在妊娠晚期和成体肺中下降，在22天表达水平最低。IGFBP-3、-4和-5的RNA丰度分布相似，与E17-E20相比，E21和E22的胎儿转录本丰度较高，E20的RNA丰度最低。IGFBP-6在早期胎肺中几乎检测不到，在胎龄E22时，转录水平比胎龄E20高10倍，在成人肺中增加35-50倍，表明这种结合蛋白在出生后肺中发挥作用。这项研究对IGF系统的肺表达进行了全面的概述，并展示了每种成分的发育调节。这些结果与IGF系统在肺发育过程中的重要作用一致，并提示IGFBPs可能是调节IGF多肽在这一过程中作用的机制。
Insulin-like growth factor (IGF)-I and IGF-II are small peptide growth factors that interact with a specific membrane receptor, the type 1 IGF receptor, to stimulate cellular proliferation and/or differentiation. The actions of these growth factors and their availability to their receptors are modulated by specific binding proteins, IGF binding protein (IGFBP)-1 through -6, which together with the IGFs and IGF receptors form the IGF system. We have analyzed RNA extracted from fetal (gestation day 16 [E16] through 22 [E22]) and adult (60-day-old) rat lung for expression of each component of the IGF system. IGF-I and -II RNAs are expressed throughout fetal development. IGF-I mRNA remained relatively constant in fetal and adult lung, whereas IGF-II RNA decreased in later gestation to levels below detection by Northern analyses in adult lung. Type 1 IGF receptor expression varied little through all ages studied, whereas the type 2 IGF receptor RNA displayed developmental regulation with a decline in expression with advancing age. IGFBP-1 transcripts were not detected in fetal or adult lung. IGFBP-2 RNA was expressed from E16 to E22, although its abundance decreased in late gestation and in adult lung, with the lowest levels of expression on day E22. IGFBP-3, -4, and -5 had similar profiles of RNA abundance, with fetuses at ages E21 and E22 displaying higher levels of transcript abundance as compared with those aged E17 to E20; the lowest RNA abundance was seen at E20. IGFBP-6, barely detectable in earlier fetal lung, increased transcript levels at fetal age E22 10-fold over fetal age E20 abundance and 35- to 50-fold in adult lung, suggesting a role for this binding protein in postnatal lung. This study presents a comprehensive overview of lung expression of the IGF system and demonstrates the developmental regulation of each component. These results are consistent with an important role for the IGF system during lung development and suggest that IGFBPs may be the mechanism for modulating the actions of the IGF peptides during this process.