Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation.

Non-antagonistic relationship between mitogenic factors and cAMP in adult Schwann cell re-differentiation.
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DOI:
10.1002/glia.20819
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发表时间:
2009-07
期刊:
影响因子:
6.2
通讯作者:
Bunge, Mary Bartlett
Bunge, Mary Bartlett
中科院分区:
医学1区
文献类型:
--
作者:
Monje, Paula V.;Rendon, Sayuri;Athauda, Gagani;Bates, Margaret;Wood, Patrick M.;Bunge, Mary Bartlett

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分离的雪旺细胞 (SC) 中环磷酸腺苷 (cAMP) 升高可诱导髓鞘形成相关基因 (MG) 的表达。为了进一步了解已知 SC 有丝分裂原在调节 SC 分化中的作用,我们研究了从成人神经中分离出的 SC 对组合 cAMP、生长因子(包括神经调节蛋白)和血清的反应。在成年 SC 中,cAMP 对 MG 的诱导与非髓磷脂形成 SC 中表达的基因的丢失以及细胞形态从双极性到扩张的上皮样形状的变化同时发生。 SC 分化的诱导需要高剂量 cAMP 刺激剂的长期治疗以及低细胞密度。用血清、单独的神经调节蛋白或其他生长因子(包括PDGF、IGF和FGF)刺激可增加SC增殖,但不诱导MG表达或相关形态学变化。最重要的是,当这些因子与 cAMP 刺激剂联合使用时,SC 增殖会协同增加,而不会降低 cAMP 的分化活性。尽管 DNA 合成的启动和分化的诱导在单个细胞中大多是不相容的事件,但 SC 能够在也支持活跃增殖的条件下分化。总体而言,结果表明,在没有神经元的情况下,cAMP 可以与生长因子信号传导同时但独立地触发 SC 再分化。
The expression of myelination-associated genes (MGs) can be induced by cyclic adenosine monophosphate (cAMP) elevation in isolated Schwann cells (SCs). To further understand the effect of known SC mitogens in the regulation of SC differentiation, we studied the response of SCs isolated from adult nerves to combined cAMP, growth factors, including neuregulin, and serum. In adult SCs, the induction of MGs by cAMP coincided with the loss of genes expressed in non-myelin-forming SCs and with a change in cell morphology from a bipolar to an expanded epithelial-like shape. Prolonged treatment with high doses of cAMP-stimulating agents, as well as low cell density, was required for the induction of SC differentiation. Stimulation with serum, neuregulin alone, or other growth factors including PDGF, IGF and FGF, increased SC proliferation but did not induce the expression of MGs or the associated morphological change. Most importantly, when these factors were administered in combination with cAMP-stimulating agents, SC proliferation was synergistically increased without reducing the differentiating activity of cAMP. Even though the initiation of DNA synthesis and the induction of differentiation were mostly incompatible events in individual cells, SCs were able to differentiate under conditions that also supported active proliferation. Overall, the results indicate that in the absence of neurons, cAMP can trigger SC re-differentiation concurrently with, but independently of, growth factor signaling.
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