Schwann cell phenotype is regulated by axon modality and central-peripheral location, and persists in vitro.

Schwann cell phenotype is regulated by axon modality and central-peripheral location, and persists in vitro.
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DOI:
10.1016/j.expneurol.2013.05.007
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发表时间:
2013-09
影响因子:
5.3
通讯作者:
Höke A
Höke A
中科院分区:
医学2区
文献类型:
--
作者:
Brushart TM;Aspalter M;Griffin JW;Redett R;Hameed H;Zhou C;Wright M;Vyas A;Höke A

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髓鞘形成的雪旺细胞表达不同的感觉和运动表型,如由它们不同的生长因子产生模式所定义的。然而,感觉和运动神经元对生长因子的异质性需求表明,许旺细胞表型可能在很宽的范围内变化。为了探索这种可能性,我们选择性地去神经支配六个离散的雪旺氏细胞群:背根,皮神经,皮肤无髓轴突,肌神经传入,肌神经传出,和腹根。对失神经支配后5、15和30天的6个靶许旺细胞群以及正常皮神经、肌神经、腹根和背根进行11种生长因子的实时RT-PCR,以建立基线表达水平。在失神经轴突群体中,IGF-1和VEGF在皮神经中表达最显著,HGF、NGF和BDNF在皮神经和背根中表达最显著,GDNF在背根和腹根中表达最显著,PTN在腹根和肌神经传出中表达最显著,IGF-2在肌神经内的传入和传出中表达最显著; CNTF、FGF-2和NT-3的表达不具有模态或位置特异性。NGF、BDNF和GDNF的ELISA证实基因表达与蛋白浓度相关。这些研究结果表明,生长因子表达失神经施万细胞不仅受到进一步的规定内先前定义的感觉和运动组,但也变化沿着的中央外周轴。髓鞘形成的雪旺细胞作为一个同质群体的传统观点是修改的认识,复杂的调节产生了各种各样的雪旺细胞表型。此外,我们发现许旺细胞表型在体外维持2周,表明它可以在没有来自轴突或基底层的指导性线索的情况下存活几次细胞分裂。
Myelinating Schwann cells express distinct sensory and motor phenotypes as defined by their differing patterns of growth factor production. The heterogeneous growth factor requirements of sensory and motor neurons, however, suggest that Schwann cell phenotype might vary across a broad spectrum. To explore this possibility, we selectively denervated six discrete Schwann cell populations: dorsal root, cutaneous nerve, cutaneous unmyelinated axons, muscle nerve afferents, muscle nerve efferents, and ventral root. Real-time RT-PCR for 11 growth factors was performed on the 6 target Schwann cell populations 5, 15, and 30 days after their denervation, and on normal cutaneous nerve, muscle nerve, ventral root, and dorsal root to establish baseline expression levels. Within the denervated axon populations, IGF-1 and VEGF were expressed most prominently in cutaneous nerve, HGF, NGF, and BDNF in cutaneous nerve and dorsal root, GDNF in dorsal root and ventral root, PTN in ventral root and muscle nerve efferents, and IGF-2 in both afferents and efferents within muscle nerve; expression of CNTF, FGF-2 and NT-3 was not modality or location specific. ELISA for NGF, BDNF, and GDNF confirmed that gene expression correlated with protein concentration. These findings demonstrate that growth factor expression by denervated Schwann cells is not only subject to further regulation within the previously-defined sensory and motor groups, but also varies along a central-peripheral axis. The traditional view of myelinating Schwann cells as a homogenous population is modified by the realization that complex regulation produces a wide variety of Schwann cell phenotypes. Additionally, we found that Schwann cell phenotype is maintained for 2 weeks in vitro, demonstrating that it may survive several cell divisions without instructive cues from either axons or basal lamina.
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