Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
J Cell Biochem. 2018 Nov;119(10):8643-8658. doi: 10.1002/jcb.27105. Epub 2018 Jun 28.
Myelin sheath is critical for the proper functioning of the peripheral nervous system (PNS), which allows the effective conduction of nerve impulses. Fibroblast growth factor 9 (FGF9) is an autocrine and paracrine protein in the fibroblast growth factor family that regulates cell differentiation and proliferation. Fgf9 Schwann cell (SC) conditional knockout mice were developed to detect the role of FGF9 in the PNS. In our study, the absence of Fgf9 led to delayed myelination in early development. The expression of mature SC-related genes decreased, and the expression of genes associated with immature SCs increased in the Fgf9 knockout mice. These data were consistent with the morphology and praxeology we observed during the development of the peripheral nerves. Extracellular-regulated kinases 1/2 (ERK1/2) are key signals for myelination, and our results showed that Fgf9 ablation led to the inactivation of ERK1/2. Further research was performed to detect the role of FGF9 in peripheral nerve injury. In superoxide dismutase 1-G93A mice with Fgf9 SC knockout, we found that Fgf9 ablation inhibited the expressions of Cd68, Il-1β, and Cd86, which contributed to the degeneration of the axon and myelin sheath.
髓鞘对于周围神经系统（PNS）的正常功能至关重要，它允许神经冲动的有效传导。成纤维细胞生长因子 9（FGF9）是成纤维细胞生长因子家族中的一种自分泌和旁分泌蛋白，可调节细胞分化和增殖。为了检测 FGF9 在 PNS 中的作用，我们构建了 Schwann 细胞（SC）条件性敲除 Fgf9 的小鼠模型。在本研究中，Fgf9 的缺失导致早期发育中的髓鞘形成延迟。成熟 SC 相关基因的表达减少，而不成熟 SC 相关基因的表达增加。这些数据与我们在周围神经发育过程中观察到的形态学和组织学相一致。细胞外调节激酶 1/2（ERK1/2）是髓鞘形成的关键信号，我们的结果表明 Fgf9 的缺失导致 ERK1/2 的失活。进一步的研究旨在检测 FGF9 在周围神经损伤中的作用。在 Schwann 细胞 Fgf9 敲除的超氧化物歧化酶 1-G93A 小鼠中，我们发现 Fgf9 的缺失抑制了 Cd68、Il-1β 和 Cd86 的表达，这有助于轴突和髓鞘的变性。
