Mews M, Meyer M
Department of Neurochemistry, Max-Planck-Institute for Psychiatry, Martinsried, Germany.
Glia. 1993 Jul;8(3):208-17. doi: 10.1002/glia.440080308.
The phenotype of a fully differentiated, mature Schwann cell is apparently largely determined by Schwann cell-axon interactions. In vitro, elevation of intracellular cAMP levels in Schwann cells induces a phenotype which resembles that of a mature, i.e., axon-related, Schwann cell. Therefore, an important role for cAMP as a second messenger of axon-Schwann cell interactions in vivo is assumed. However, the effects of cAMP on Schwann cells are not restricted to induction of features of a mature phenotype. For example, elevation of intracellular cAMP levels results also in a markedly increased synthesis of nerve growth factor (NGF) mRNA, which is barely detectable in intact sciatic nerves of adult animals. Furthermore, since cAMP induces myelin gene expression in cultured Schwann cells, additional regulatory mechanisms have to be postulated for the induction and maintenance of a mature non-myelinating Schwann cell phenotype. Here we show that a soluble protein "growth factor" can partially induce a non-myelinating nature Schwann cell phenotype in vitro. Treatment with transforming growth factor beta 1 (TGF-beta 1) results in a marked and rapid downregulation of the low affinity NGF receptor (NGFR) on cultured Schwann cells without induction of P0 gene expression. In contrast, in agreement with previous studies, an increase in P0 mRNA levels and a reduction in NGFR mRNA levels are observed after cAMP elevation. Downregulation of NGFR mRNA after cAMP elevation is much slower when compared with the effect of TGF-beta 1, suggesting the involvement of different intracellular mechanisms. Consistent with this hypothesis, we did not observe an induction of mRNA coding for TGF-beta isoforms after cAMP elevation in cultured Schwann cells which constitutively synthesize TGF-beta 1 mRNA.
完全分化成熟的施万细胞的表型显然在很大程度上由施万细胞 - 轴突相互作用决定。在体外，提高施万细胞内的cAMP水平会诱导出一种类似于成熟的、即与轴突相关的施万细胞的表型。因此，假定cAMP在体内作为轴突 - 施万细胞相互作用的第二信使发挥重要作用。然而，cAMP对施万细胞的作用并不局限于诱导成熟表型的特征。例如，细胞内cAMP水平的升高还会导致神经生长因子（NGF）mRNA的合成显著增加，而在成年动物完整的坐骨神经中几乎检测不到这种mRNA。此外，由于cAMP在培养的施万细胞中诱导髓磷脂基因表达，因此必须假定存在其他调节机制来诱导和维持成熟的非髓鞘形成施万细胞表型。在这里，我们表明一种可溶性蛋白质“生长因子”可以在体外部分诱导非髓鞘形成性质的施万细胞表型。用转化生长因子β1（TGF-β1）处理会导致培养的施万细胞上低亲和力NGF受体（NGFR）显著且快速下调，而不会诱导P0基因表达。相反，与先前的研究一致，cAMP升高后观察到P0 mRNA水平增加和NGFR mRNA水平降低。与TGF-β1的作用相比，cAMP升高后NGFR mRNA的下调要慢得多，这表明涉及不同的细胞内机制。与这一假设一致，在持续合成TGF-β1 mRNA的培养施万细胞中，cAMP升高后我们未观察到编码TGF-β同工型的mRNA的诱导。
