Involvement of IGF-2, IGF-1R, IGF-2R and PTEN in development of human tooth germ - an immunohistochemical study
Involvement of IGF-2, IGF-1R, IGF-2R and PTEN in development of human tooth germ - an immunohistochemical study
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DOI：
10.1080/15476278.2016.1197460
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发表时间：
2016-01-01
期刊：
影响因子：
2.3
通讯作者：
Saraga-Babic, Mirna
中科院分区：
文献类型：
--
作者：
Kero, Darko;Cigic, Livia;Saraga-Babic, Mirna
胰岛素样生长因子2（IGF-2）是一种对产前生长和发育至关重要的肽类激素。IGF-2通过胰岛素样生长因子1受体（IGF-1 R）发挥其促有丝分裂作用，并通过与胰岛素样生长受体2（IGF-2 R）结合而消除。IGF-2也受磷酸酶和张力蛋白同源物（PTEN）负调节，所述磷酸酶和张力蛋白同源物是在各种肿瘤中突变的磷酸酶。在人类牙齿发生过程中，这些因素之间的相互作用知之甚少。本研究采用免疫荧光双标记技术，分析了IGF-2、IGF-1 R、IGF-2 R和PTEN在胎龄7 ~ 20周人切牙牙胚发育过程中的表达模式。IGF-2主要表达于成釉器，而PTEN在牙乳头和部分成釉器中有轻度至中度表达。IGF-1 R的表达是无处不在的，并显示出强强度在整个成釉器官。而IGF-2 R在成釉器和牙乳头中的表达则无规律可循。IGF-2、IGF-1 R、IGF-2 R和PTEN在高度增殖的颈环中的表达模式，以及在成釉器获得最终形状的钟状期早期和晚期尖突区的前成釉细胞和前成牙本质细胞的分化中的表达模式，表明这些因子在人切牙冠形态发生中的重要性。两者合计，我们的数据表明，IGF-2，IGF-1 R，IGF-2 R和PTEN的参与在正常牙齿发育过程中的基本细胞过程（增殖，分化）的时空模式。它们也与提高人类牙齿发生的分子基础的知识有关。
Insulin-Like Growth Factor 2 (IGF-2) is a peptide hormone essential for prenatal growth and development. IGF-2 exerts its mitogenic effects via Insulin-Like Growth Factor 1 Receptor (IGF-1R), and is eliminated by binding to Insulin-Like Growth Receptor 2 (IGF-2R). IGF-2 is also negatively regulated by Phosphatase and Tensin Homolog (PTEN), a phosphatase mutated in various tumors. Not much is known about the interplay between these factors during human odontogenesis. In this study, expression patterns of IGF-2, IGF-1R, IGF-2R and PTEN were analyzed by double immunofluorescence in incisor human tooth germs during the foetal period of development between the 7(th) and 20(th) gestational week. Throughout the investigated period, IGF-2 was mostly expressed in enamel organ, whereas mild to moderate expression of PTEN could be seen in dental papilla and parts of enamel organ. Expression of IGF-1R was ubiquitous and displayed strong intensity throughout the entire enamel organ. In contrast, expression of IGF-2R had rather erratic pattern in enamel organ and dental papilla alike. Expression patterns of IGF-2, IGF-1R, IGF-2R and PTEN in highly proliferative cervical loops, as well as in differentiating pre-ameloblasts and pre-odontoblasts of cusp tip region during the early and late bell stages when enamel organ acquires definitive shape, indicate importance of these factors in crown morphogenesis of human incisor. Taken together, our data suggest the involvement of IGF-2, IGF-1R, IGF-2R and PTEN in temporo-spatial patterning of basic cellular processes (proliferation, differentiation) during normal tooth development. They are also relevant for improving knowledge of molecular basis of human odontogenesis.