Scherer S S, Wang D Y, Kuhn R, Lemke G, Wrabetz L, Kamholz J
Department of Neurology, Hospital of University of Pennsylvania, Philadelphia 19104.
J Neurosci. 1994 Apr;14(4):1930-42. doi: 10.1523/JNEUROSCI.14-04-01930.1994.
SCIP (suppressed cAMP-inducible POU) is a POU domain transcription factor expressed by Schwann cells. Drugs that elevate intracellular cAMP, such as forskolin, increase the expression of SCIP and partially mimic the inductive effects of axons on Schwann cell gene expression. Thus, SCIP may be involved in a differentiation pathway in Schwann cells that is activated by axons. We have examined this issue by studying SCIP expression in developing, degenerating, and regenerating rat peripheral nerves, and in Schwann cell-neuron cocultures. High levels of SCIP mRNA were detected in developing and regenerating nerves, and axotomy at these times caused the level of SCIP mRNA to plummet. Similarly, there were many SCIP-immunoreactive Schwann cell nuclei in developing and regenerating nerves, and their number fell sharply after axotomy. SCIP-immunoreactive Schwann cells were associated with axons in developing and regenerating nerves, and in Schwann cell-neuron cocultures. These data demonstrate that axons upregulate the expression of SCIP in Schwann cells, and that SCIP is expressed in Schwann cells that ensheathe axons. Thus, SCIP may mediate some of the changes in Schwann cell gene expression that accompany axonal ensheathment.
SCIP(抑制性cAMP诱导性POU)是一种由施万细胞表达的POU结构域转录因子。能提高细胞内cAMP水平的药物,如毛喉素,可增加SCIP的表达,并部分模拟轴突对施万细胞基因表达的诱导作用。因此,SCIP可能参与了由轴突激活的施万细胞分化途径。我们通过研究发育中、退变中和再生中的大鼠周围神经以及施万细胞-神经元共培养物中的SCIP表达来探讨这个问题。在发育中和再生中的神经中检测到高水平的SCIP mRNA,此时进行轴突切断会导致SCIP mRNA水平急剧下降。同样,在发育中和再生中的神经中有许多SCIP免疫反应阳性的施万细胞核,轴突切断后其数量急剧减少。在发育中和再生中的神经以及施万细胞-神经元共培养物中,SCIP免疫反应阳性的施万细胞与轴突相关。这些数据表明轴突上调施万细胞中SCIP的表达,并且SCIP在包裹轴突的施万细胞中表达。因此,SCIP可能介导了伴随轴突包裹的施万细胞基因表达的一些变化。