Cellular localization of messenger RNAs for insulin-like growth factors (IGFs), their receptors and binding proteins during fetal rat lung development
Cellular localization of messenger RNAs for insulin-like growth factors (IGFs), their receptors and binding proteins during fetal rat lung development
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DOI：
10.1165/ajrcmb.14.1.8534487
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发表时间：
1996-01-01
影响因子：
6.4
通讯作者：
Stiles, AD
中科院分区：
文献类型：
--
作者：
RetschBogart, GZ;MoatsStaats, BM;Stiles, AD
为了深入了解胰岛素样生长因子（IGFs）在调节肺发育中的作用，我们使用原位杂交组织化学（ISHH）检查了妊娠15至21天胎鼠肺中IGF-I和IGF-II、IGF结合蛋白（IGFBP-1至IGFBP-6）和IGF细胞表面受体的个体发育和表达部位。IGF-I和IGF-II mRNA在整个发育期间表达，表观丰度变化不大，IGF-I mRNA定位于间充质细胞，特别是气道上皮周围的细胞，而IGF-II mRNA，这是更丰富，主要定位于上皮细胞。1型IGF受体（可能介导两种IGF作用的受体）在几乎所有细胞中广泛表达，而2型IGF受体（被认为参与IGF内化和降解）的表达仅限于肺内血管的间充质和中层。与IGFs一样，通过胎儿发育，IGF受体mRNA的丰度几乎没有明显变化，2型IGF受体mRNA更丰富。IGFBPs的表达在肺发育过程中有明显变化。IGFBP-2、IGFBP-3、IGFBP-4和IGFBP-5从妊娠第15天开始表达，但它们的表达位点和个体发育不同。IGFBP-2 mRNA的表达丰富，并在整个妊娠期恒定，仅限于近端和远端气道上皮。IGFBP-3和IGFBP-5也在近端气道上皮中表达，但在间质和血管周围间质中也表现出显著的表达。两者的丰度随着妊娠进展而增加（IGFBP-5大于IGFBP-3）。IGFBP-4 mRNA仅表达于间质中，其丰度在妊娠第16 ~ 19天达到高峰。我们没有发现IGFBP-1或IGFBP-6表达的证据。我们得出结论，IGF-I、IGF-II和1型IGF受体在整个妊娠期间在肺中的表达支持IGFs在肺生长和发育中的作用。IGFBP表达的复杂模式（不同的表达位点和个体发育）表明IGFBP在特定的靶位点调节IGF作用。此外，由于在胎儿肺发育过程中IGF或IGF受体mRNA的表达几乎没有变化，因此IGFBP表达的调节可能对肺发育过程中IGF作用的控制至关重要。
To gain insight into the role of the insulin-like growth factors (IGFs) in regulating lung development, we have used in situ hybridization histochemistry (ISHH) to examine the ontogeny and sites of expression of IGF-I and IGF-II, IGF binding proteins (IGFBP-1 to IGFBP-6), and IGF cell surface receptors in fetal rat lung from 15 to 21 days of gestation. Both IGF-I and IGF-II mRNAs were expressed throughout the developmental period studied with little change in apparent abundance, IGF-I mRNA localized to mesenchymal cells, especially those surrounding airway epithelium, while IGF-II mRNA, which was somewhat more abundant, localized predominantly to epithelia. The type 1 IGF receptor, the receptor that likely mediates the actions of both IGFs, was expressed widely in virtually all cells, whereas the expression of the type 2 IGF receptor, thought to be involved in IGF internalization and degradation, was confined to the mesenchyme and medial layers of intrapulmonary vessels. As with the IGFs, there was little apparent change in the abundance of IGF receptor mRNAs through fetal development, and the type 2 IGF receptor mRNA was more abundant. The expression of IGFBPs changed significantly during lung development. IGFBP-2, -3, -4, and -5 were expressed from day 15 of gestation, but their sites of expression and ontogeny differed. IGFBP-2 mRNA expression was abundant and constant throughout gestation and was confined to proximal and distal airway epithelia. IGFBP-3 and IGFBP-5 also were expressed by proximal airway epithelia, but also exhibited significant expression in interstitial mesenchyme and in mesenchyme surrounding vessels. The abundance of both increased as gestation progressed (IGFBP-5 greater than IGFBP-3). IGFBP-4 mRNA was confined to interstitial mesenchyme and its abundance peaked at days 16 to 19 of gestation. We found no evidence for expression of either IGFBP-1 or IGFBP-6 We conclude that the expression of IGF-I, IGF-II, and the type 1 IGF receptor throughout gestation in the lung supports a role for the IGFs in lung growth and development. The complex pattern of IGFBP expression (differing sites and ontogeny of expression) suggests that the IGFBPs modulate IGF actions at specific target sites. Furthermore, because there is little change in the expression of IGFs or IGF receptor mRNAs during fetal lung development, regulation of IGFBP expression may be essential to the control of IGF actions during lung development.