Calcitonin gene-related peptide promotes Schwann cell proliferation.

Calcitonin gene-related peptide promotes Schwann cell proliferation.
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降钙素基因相关肽促进雪旺细胞增殖。

DOI:
10.1083/jcb.129.3.789
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发表时间:
1995-05
影响因子:
7.8
通讯作者:
Mudge, A W
Mudge, A W
中科院分区:
生物学1区
文献类型:
--
作者:
Cheng, L;Khan, M;Mudge, A W

文献摘要

被引文献

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培养中的雪旺细胞在有丝分裂原如PDGF和胶质生长因子(GGF)的作用下发生分裂,但如果在添加PDGF或GGF的同时加入可增加雪旺细胞内cAMP的forskolin等制剂,则增殖能力会大大增强(Davis, J. B. and P. Stroobant, 1990)。[j] .细胞生物学杂志。福斯克林的作用可能是由于PDGF受体数量的增加(Weinmaster, G., and G. Lemke, 1990)。EMBO(欧元。摩尔。杂志。器官)。j . 9:915 - 920。据报道,神经肽和β -肾上腺素能激动剂对增强PDGF或GGF的有丝分裂反应没有作用。我们发现神经肽降钙素基因相关肽(CGRP)增加了雪旺细胞cAMP水平,但细胞迅速脱敏。因此,我们以脉动方式刺激细胞以部分克服脱敏的影响,并表明CGRP可以与PDGF协同刺激雪旺细胞增殖,并且在脉动状态下CGRP与福斯克林一样有效。CGRP是中性内肽酶24.11的良好底物。在体内的雪旺细胞表面有这种蛋白酶,因此CGRP的作用可以被这种酶终止,从而防止脱敏。因此,我们认为CGRP可能通过调节PDGF等有丝分裂因子的反应,在刺激雪旺细胞增殖中发挥重要作用。
Schwann cells in culture divide in response to defined mitogens such as PDGF and glial growth factor (GGF), but proliferation is greatly enhanced if agents such as forskolin, which increases Schwann cell intracellular cAMP, are added at the same time as PDGF or GGF (Davis, J. B., and P. Stroobant. 1990. J. Cell Biol. 110:1353-1360). The effect of forskolin is probably due to an increase in numbers of PDGF receptors (Weinmaster, G., and G. Lemke. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:915-920. Neuropeptides and beta-adrenergic agonists have been reported to have no effect on potentiating the mitogenic response of either PDGF or GGF. We show that the neuropeptide calcitonin gene- related peptide (CGRP) increases Schwann cell cAMP levels, but the cells rapidly desensitize. We therefore stimulated the cells in pulsatile fashion to partly overcome the effects of desensitization and show that CGRP can synergize with PDGF to stimulate Schwann cell proliferation, and that CGRP is as effective as forskolin in the pulsatile regime. CGRP is a good substrate for the neutral endopeptidase 24.11. Schwann cells in vivo have this protease on their surface, so the action of CGRP could be terminated by this enzyme and desensitization prevented. We therefore suggest that CGRP may play an important role in stimulating Schwann cell proliferation by regulating the response of mitogenic factors such as PDGF.