Igf2 deficiency results in delayed lung development at the end of gestation
Igf2 deficiency results in delayed lung development at the end of gestation
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DOI：
10.1210/en.2006-0498
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发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Lopez, Mary Frances
中科院分区：
文献类型：
--
作者：
Silva, Delia;Venihaki, Maria;Lopez, Mary Frances
IGF-II是与胰岛素和IGF-I具有结构同源性的多肽激素。IGF-II在胎儿生长中起重要作用，因为IGF-II基因（Igf 2）靶向破坏的小鼠表现出严重的生长迟缓。IGFs在胎儿肺中的作用已经被几项研究所证实，包括那些已经确定IGF mRNA表达的研究，以及在不同发育阶段肺中IGF受体和结合蛋白的表达。在这项研究中，我们使用携带Igf 2无效突变的小鼠（Igf 2（-/-）小鼠）来确定IGF-II的缺失是否对胎肺成熟有任何影响。结果表明，在孕17.5和18.5天，Igf 2（-/-）胎儿的肺泡间隔较Igf 2（+/+）胎儿的肺泡间隔增厚，肺泡结构紊乱。这些形态学改变可能是暴露于较低水平的糖皮质激素的结果，因为与野生型对照相比，Igf 2（-/-）母亲的血浆皮质酮水平显著降低。为了支持这一点，来自纯合子敲除交配的胎儿，其中母亲用15 μ g/ml皮质酮处理，从杂合子交配获得的Igf 2（-/-）胎儿具有与野生型胎儿相似的肺组织学。最后，我们发现，IGF-I和SP-B mRNA水平上调，在肺中的Igf 2（-/-）胎儿在妊娠结束。这项研究表明，Igf 2在胎儿肺的发育中起着重要的作用，并可能通过调节母体因素，如皮质酮水平，在怀孕期间影响胎儿肺的成熟。
IGF-II is a polypeptide hormone with structural homology to insulin and IGF-I. IGF-II plays an important role in fetal growth as mice with targeted disruption of the IGF-II gene (Igf2)exhibit severe growth retardation. The role of IGFs in the fetal lung has been suggested by several studies, including those that have identified IGF mRNA expression, and that of their receptors and binding proteins in the lungs at different stages of development. In this study, we used mice carrying a null mutation of Igf2 (Igf2(-/-) mice) to determine whether the absence of IGF-II had any effect in fetal lung maturation. Our results showed that the lungs of Igf2(-/-) fetuses had thicker alveolar septae and poorly organized alveoli when compared with those of Igf2(+/+) on d 17.5 and 18.5 of gestation. These morphological alterations may be the result of exposure to lower levels of glucocorticoids because plasma corticosterone levels were significantly lower in Igf2(-/-) mothers compared with wild-type controls. In support of this, fetuses from homozygous knockout matings, where mothers were treated with 15 mu g/ml corticosterone, and Igf2(-/-) fetuses obtained from heterozygous matings had similar lung histology to those of wild-type fetuses. Finally, we found that IGF-I and SP-B mRNA levels were up-regulated in the lungs of Igf2(-/-) fetuses at the end of gestation. This study suggests that Igf2 plays an important role in the development of the fetal lung and may affect fetal lung maturation by regulating maternal factors, such as corticosterone levels, during pregnancy.