De-Fraja C, Conti L, Magrassi L, Govoni S, Cattaneo E
Institute of Pharmacological Sciences, University of Milan, Italy.
J Neurosci Res. 1998 Nov 1;54(3):320-30. doi: 10.1002/(SICI)1097-4547(19981101)54:3<320::AID-JNR3>3.0.CO;2-R.
The presence and activation of members of the Janus Kinases/Signal Transducers and Activator of Transcription proteins in response to specific cytokines is currently the focus of intense investigation in the hematopoietic system. Although some evidence suggests that cytokines might play an important role in brain development and brain pathologies, very limited information is available on the presence of the JAK/STAT proteins in the Central Nervous System. Here we provide Western blot and immunohistochemistry data on the presence of Jak2 in vivo in the immature brain, its expression being greater in early stages of the embryonic life and gradually diminishing towards adulthood. Conversely, Jak1 was found expressed at a lower level compared to Jak2 and not modulated during brain maturation. Western blot data also show that specific members of the STAT family, the cytoplasmic substrates of the Janus Kinases, are present in vivo and that the extent of their expression is modulated differently at various stages. In particular, Stat6 protein levels were markedly attenuated at advanced stages of differentiation, as well as in the adult brain, with respect to early embryonic life. On the contrary, Stat3 levels did not vary. Analysis of Statl and Stat5 proteins showed a more complex expression pattern. These data indicate that members of the JAK/STAT proteins are present and modulated in vivo in the embryonic and postnatal brain, therefore supporting their role in the modulation of gene expression during the different stages of brain maturation.
在造血系统中，针对特定细胞因子，Janus激酶/信号转导子和转录激活子蛋白成员的存在及激活情况，目前是深入研究的焦点。尽管有一些证据表明细胞因子可能在脑发育和脑部病变中发挥重要作用，但关于中枢神经系统中JAK/STAT蛋白的存在情况，现有信息非常有限。在此，我们提供了关于未成熟脑中Jak2在体内存在情况的蛋白质印迹法和免疫组织化学数据，其表达在胚胎生命早期较高，随着成年逐渐减少。相反，与Jak2相比，Jak1的表达水平较低，且在脑成熟过程中未受调节。蛋白质印迹法数据还显示，Janus激酶的细胞质底物——STAT家族的特定成员在体内存在，且其表达程度在不同阶段受到不同调节。特别是，与早期胚胎生命相比，Stat6蛋白水平在分化后期以及成年脑中显著降低。相反，Stat3水平没有变化。对Stat1和Stat5蛋白的分析显示出更复杂的表达模式。这些数据表明，JAK/STAT蛋白成员在胚胎期和出生后的脑中存在并受到调节，因此支持它们在脑成熟不同阶段基因表达调节中的作用。
