Johns Hopkins Dept of Orthopaedics, 601N. Caroline St., Baltimore, MD 21287, USA.
Exp Neurol. 2013 Sep;247:272-81. doi: 10.1016/j.expneurol.2013.05.007. Epub 2013 May 21.
Myelinating Schwann cells express distinct sensory and motor phenotypes as defined by their differing patterns of growth factor production (Hoke et al., 2006). 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 the 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.
施万细胞表达独特的感觉和运动表型，这由它们不同的生长因子产生模式来定义（Hoke 等人，2006 年）。然而，感觉和运动神经元的异质生长因子需求表明，施万细胞表型可能在广泛的范围内变化。为了探索这种可能性，我们选择性地去神经支配了六个离散的施万细胞群体：背根、皮肤神经、皮肤无髓轴突、肌肉神经传入纤维、肌肉神经传出纤维和腹根。在去神经支配后 5、15 和 30 天，对 6 个靶标施万细胞群体进行了 11 种生长因子的实时 RT-PCR，同时对正常皮肤神经、肌肉神经、腹根和背根进行了检测，以确定其基础表达水平。在去神经的轴突群体中，IGF-1 和 VEGF 在皮肤神经中表达最为明显，HGF、NGF 和 BDNF 在皮肤神经和背根中表达，GDNF 在背根和腹根中表达，PTN 在腹根和肌肉神经传出纤维中表达，IGF-2 在肌肉神经传入和传出纤维中表达；CNTF、FGF-2 和 NT-3 的表达没有特定的模态或位置。NGF、BDNF 和 GDNF 的 ELISA 证实了基因表达与蛋白浓度相关。这些发现表明，去神经支配的施万细胞的生长因子表达不仅受到先前定义的感觉和运动群体内的进一步调节，而且还沿着中央-外周轴变化。有髓施万细胞作为一个同质群体的传统观点被修改为，复杂的调节产生了各种各样的施万细胞表型。此外，我们发现施万细胞表型在体外保持 2 周，表明它可以在没有轴突或基底膜的指导线索的情况下存活几个细胞分裂。
