EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR RECEPTOR-1 AND RECEPTOR-2 IN THE DEVELOPING LUNG AND THEIR RELATION TO EPITHELIAL-CELL DIFFERENTIATION
EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR RECEPTOR-1 AND RECEPTOR-2 IN THE DEVELOPING LUNG AND THEIR RELATION TO EPITHELIAL-CELL DIFFERENTIATION
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DOI：
10.1165/ajrcmb.13.3.7654382
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发表时间：
1995-09-01
影响因子：
6.4
通讯作者：
BRODY, JS
中科院分区：
文献类型：
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作者：
MAITRE, B;CLEMENT, A;BRODY, JS
胰岛素样生长因子(IGF)及其受体在许多系统中被认为是细胞分化和细胞增殖的调节因子，并被证明在胚胎发育中发挥重要作用。在本研究中，我们用聚合酶链式反应(PCR)检测了IGF-I和IGF-II、IGF结合蛋白2(IGFBP-2)、IGF受体1(IGFR-1)和IGFR-2(IGFR-2)在胎肺发育以及出生后早期和成人肺中的表达。与IGFBP-2一样，IGF-I在胚胎和出生后各年龄段的肺中均有表达，而IGF-II只在出生前的肺中表达。用聚合酶链式反应和原位杂交的方法检测到IGFR-1在妊娠14天的肺上皮细胞中表达，但在18天时未见表达。肺泡上皮细胞在出生后早期可重新表达IGFR-1mRNA，但在成人肺中不表达。用聚合酶链式反应和原位杂交方法检测到IGFR-2在出生后14天的胚胎上皮细胞中有表达，在出生后18天和出生时未见表达，但在出生后早期的肺泡壁中有高水平的重新表达。免疫细胞化学定位证实IGFR-2在胎儿晚期和新生儿肺中缺失。它在肺泡中重新出现，仅在1型细胞中出现，在出生后早期和成年肺中出现。这些研究表明，IGF受体在发育中和出生后的肺中具有阶段和细胞特异性的出现。他们还建立了IGFR-2作为成熟的肺泡1型细胞的标志。IGFR-2在未分化的高度增殖的胚胎上皮细胞和分化的、非增殖的肺泡1型细胞中的出现表明，该受体在肺发育的极端阶段发挥着两种不同的功能。当肺中不存在IGF-II时，IGFR-2出现在I型细胞中，这表明该受体在I型细胞中起着与IGF-II无关的功能。
Insulin-like growth factors (IGFs) and their receptors have been implicated as regulators of cell differentiation and cell proliferation in a number of systems and have been shown to play an important role in embryonic development. In this study we examined expression of mRNA for IGF-I and IGF-II, IGF binding protein 2 (IGFBP-2), and IGF receptors 1 (IGFR-1) and 2 (IGFR-2) during fetal lung development and in early postnatal and adult lungs by the polymerase chain reaction (PCR). IGF-I mRNA was found in embryonic and postnatal lungs at all ages as was IGFBP-2, whereas IGF-II mRNA was present only in prenatal lungs. IGFR-1 was present in all but the adult lungs, Lung epithelial cells expressed IGFR-1 at 14 days' gestation but not at 18 days' gestation as measured by PCR and in situ hybridization. Alveolar epithelial cells re-expressed IGFR-1 mRNA in the early postnatal period but not in the adult lung. IGFR-2 was expressed by PCR and in situ hybridization in 14-day embryonic epithelium, was not present at 18 days or at birth, but was re-expressed at high levels in the early postnatal alveolar wall. Immunocytochemical localization of IGFR-2 confirmed its absence in the late fetal and newborn lung. It reappeared in alveoli, exclusively in type 1 cells, in early postnatal and adult lungs. These studies demonstrate the stage-and cell-specific appearance ofIGF receptors in the developing and postnatal lung. They also establish IGFR-2 as a marker of the mature alveolar type 1 cell. The appearance of IGFR-2 in undifferentiated highly proliferative embryonic epithelial cells and in differentiated, nonproliferating alveolar type 1 cells suggests that this receptor serves two different functions at the extremes of lung development. The appearance of IGFR-2 in type 1 cells at a time when no IGF-II is present in the lung suggests that this receptor serves a function unrelated to IGF-II in the type I cell.