He Qianru, Shen Mi, Tong Fang, Cong Meng, Zhang Shibo, Gong Yanpei, Ding Fei
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, China.
Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, China.
Front Neurosci. 2019 Jan 9;12:1016. doi: 10.3389/fnins.2018.01016. eCollection 2018.
Fibroblasts (Fbs) effectively promote Schwann cells (SCs) migration, proliferation, and neurite regeneration. Whether Fbs express different motor and sensory phenotypes that regulate the cell behavior and peripheral nerve function has not been elucidated. The present study utilized the whole rat genome microarray analysis and identified a total of 121 differentially expressed genes between the primary cultured motor and sensory Fbs. The genes with high expression in sensory Fbs were related to proliferation, migration, chemotaxis, motility activation, protein maturation, defense response, immune system, taxis, and regionalization, while those with high expression in motor Fbs were related to neuron differentiation, segmentation, and pattern specification. Thus, the significant difference in the expression of some key genes was found to be associated with cell migration and proliferation, which was further validated by quantitative real-time PCR (qPCR). The cell proliferation or migration analysis revealed a higher rate of cell migration and proliferation of sensory Fbs than motor Fbs. Moreover, the downregulated expression of chemokine (C-X-C motif) ligand 10 (CXCL10) and chemokine (C-X-C motif) ligand 3 (CXCL3) suppressed the proliferation rate of sensory Fbs, while it enhanced that of the motor Fbs. However, the migration rate of both Fbs was suppressed by the downregulated expression of CXCL10 or CXCL3. Furthermore, a higher proportion of motor or sensory SCs migrated toward their respective (motor or sensory) Fbs; however, few motor or sensory SCs co-cultured with the other type of Fbs (sensory or motor, respectively), migrated toward the Fbs. The current findings indicated that Fbs expressed the distinct motor and sensory phenotypes involved in different patterns of gene expression, biological processes, and effects on SCs. Thus, this study would provide insights into the biological differences between motor and sensory Fbs, including the role in peripheral nerve regeneration.
成纤维细胞(Fbs)可有效促进雪旺细胞(SCs)迁移、增殖和神经突再生。成纤维细胞是否表达不同的运动和感觉表型来调节细胞行为和周围神经功能尚未阐明。本研究利用全大鼠基因组微阵列分析,确定了原代培养的运动和成纤维细胞之间总共121个差异表达基因。在感觉成纤维细胞中高表达的基因与增殖、迁移、趋化性、运动激活、蛋白质成熟、防御反应、免疫系统、趋性和区域化有关,而在运动成纤维细胞中高表达的基因与神经元分化、分割和模式规范有关。因此,发现一些关键基因表达的显著差异与细胞迁移和增殖有关,这通过定量实时PCR(qPCR)进一步得到验证。细胞增殖或迁移分析显示,感觉成纤维细胞的细胞迁移和增殖率高于运动成纤维细胞。此外,趋化因子(C-X-C基序)配体10(CXCL10)和趋化因子(C-X-C基序)配体3(CXCL3)的表达下调抑制了感觉成纤维细胞的增殖率,而增强了运动成纤维细胞的增殖率。然而,CXCL10或CXCL3表达下调均抑制了两种成纤维细胞的迁移率。此外,更高比例的运动或感觉雪旺细胞向各自(运动或感觉)的成纤维细胞迁移;然而,与另一种类型的成纤维细胞(分别为感觉或运动)共培养的运动或感觉雪旺细胞很少向该成纤维细胞迁移。目前的研究结果表明,成纤维细胞表达了不同的运动和感觉表型,这些表型参与了不同的基因表达模式、生物学过程以及对雪旺细胞的影响。因此,本研究将为运动和感觉成纤维细胞之间的生物学差异提供见解,包括在周围神经再生中的作用。