GGF/neuregulin induces a phenotypic reversion of oligodendrocytes
GGF/neuregulin induces a phenotypic reversion of oligodendrocytes
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DOI：
10.1006/mcne.1998.0733
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发表时间：
1999-02-01
影响因子：
3.5
通讯作者：
Salzer, JL
中科院分区：
文献类型：
--
作者：
Canoll, PD;Kraemer, R;Salzer, JL
我们先前已经表明，神经胶质生长因子（GGF），神经调节蛋白（NRG）家族的生长因子的一个成员，是细胞培养物中少突胶质祖细胞的有丝分裂原和存活因子，并且在前少突胶质细胞阶段阻断它们的分化（P. D. Canoll等人，1996，Neuron 17，229-243）。我们现在表明，GGF是能够诱导分化的少突胶质细胞进行表型逆转，其特征是由MBP表达的损失，重新表达的中间丝蛋白巢蛋白，重组的肌动蛋白细胞骨架，和一个显着减少的过程中的数量每细胞。TUNEL分析表明，GGF是成熟的少突胶质细胞没有细胞毒性，而是提高他们的生存。GGF还诱导PI 3-激酶和MAP激酶信号通路的快速激活。这些结果进一步支持了NRG在促进少突胶质细胞谱系中细胞的增殖和存活以及抑制其分化中的作用，并证明了在培养中分化的少突胶质细胞保留了相当程度的表型可塑性。
We have previously shown that glial growth factor (GGF), a member of the neuregulin (NRG) family of growth factors, isa mitogen and survival factor for oligodendrocyte progenitors in cell culture and blocks their differentiation at the pro-oligodendrocyte stage (P. D. Canoll et al., 1996, Neuron 17, 229-243). We now show that GGF is able to induce differentiated oligodendrocytes to undergo a phenotypic reversion characterized by loss of MBP expression, reexpression of the intermediate filament protein nestin, reorganization of the actin cytoskeleton, and a dramatic reduction in the number of processes per cell. TUNEL analysis demonstrates that GGF is not cytotoxic for mature oligodendrocytes, but rather enhances their survival. GGF also induces the rapid activation of the PI 3-kinase and MAP kinase signaling pathways. These results further support a role for the NRGs in promoting the proliferation and survival of and inhibiting the differentiation of cells in the oligodendrocyte lineage and demonstrate that oligodendrocytes that differentiate in culture retain a substantial degree of phenotypic plasticity.