Platelet-derived growth factors and fibroblast growth factors are mitogens for rat Schwann cells.

Platelet-derived growth factors and fibroblast growth factors are mitogens for rat Schwann cells.
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血小板衍生的生长因子和成纤维细胞生长因子是大鼠雪水细胞的有丝分裂因子。

DOI:
10.1083/jcb.110.4.1353
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发表时间:
1990-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Stroobant P
Stroobant P
中科院分区:
其他
文献类型:
--
作者:
Davis JB;Stroobant P

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培养的大鼠坐骨神经雪旺细胞对有限范围的促有丝分裂剂(包括胶质生长因子、转化生长因子β-1和β-2(TGF-β 1、TGF-β 2)、一些细胞膜相关因子)和提高细胞内cAMP水平的试剂(如霍乱毒素和毛喉素)有反应。这些反应需要FCS的存在,在没有其他因子的情况下,FCS表现出很少或没有促有丝分裂活性。然而,我们最近发现,毛喉素大大增强了促有丝分裂信号从TGF-β 1和β 2,提高了可能性,cAMP可能耦合其他因素的有丝分裂。因此,我们已经筛选了一系列的候选有丝分裂原使用DNA合成测定。除了TGF-β和神经胶质生长因子外,在单独10%血清存在下,所测试的因子均不具有促有丝分裂作用。然而,随着福司可林的加入,猪PDGF、人PDGF、酸性和碱性FGF是大鼠雪旺细胞的有效有丝分裂原,刺激DNA合成并增加细胞数量。霍乱毒素和dibutyrylcyclicAMP,但不是1,9-dideoxyforskolin,可以取代forskolin,表明促有丝分裂作用是通过腺苷酸环化酶激活介导的。猪PDGF在15 pM时产生半数最大刺激,人PGDF在1 nM时产生同等反应.碱性FGF在5 pM时为最大值的一半,酸性FGF在1 nM时为最大值的一半。PDGFs和FGFs作为雪旺细胞的有丝分裂原的识别对于雪旺细胞在神经发育和再生中的增殖以及雪旺细胞肿瘤发生的研究具有许多意义。
Rat sciatic nerve Schwann cells in culture respond to a limited range of mitogens, including glial growth factor, transforming growth factors beta-1 and beta-2 (TGF-beta 1, TGF-beta 2), some cell membrane- associated factors, and to agents such as cholera toxin and forskolin which raise intracellular levels of cAMP. These responses require the presence of FCS, which exhibits little or no mitogenic activity in the absence of other factors. However, we recently found that forskolin greatly potentiates the mitogenic signal from TGFs-beta 1 and beta 2, raising the possibility that cAMP might couple other factors to mitogenesis. We have therefore screened a range of candidate mitogens using DNA synthesis assays. Other than TGFs-beta and glial growth factor, none of the factors tested were mitogenic in the presence of 10% serum alone. With the addition of forskolin, however, porcine PDGF, human PDGF, acidic and basic FGF were potent mitogens for rat Schwann cells, stimulating DNA synthesis and increasing cell number. Cholera toxin and dibutyrylcyclicAMP, but not 1,9-dideoxyforskolin, can substitute for forskolin indicating that the mitogenic effect is mediated via adenylyl cyclase activation. Porcine PDGF gave half- maximal stimulation at 15 pM, and human PGDF an equivalent response at 1 nM. Basic FGF was half maximal at 5 pM, acidic FGF at 1 nM. The recognition of PDGFs and FGFs as mitogens for Schwann cells has many implications for the study of Schwann cell proliferation in the development and regeneration of nerves, and in Schwann cell tumorigenesis.