He Qianru, Cheng Zhenghang, Zhou Qiang, Tong Fang, Li Yan, Zhou Xinyang, Yu Miaomei, Ji Yuhua, Ding Fei
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, JS 226001, China.
State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200433, China.
Exp Neurol. 2023 Mar;361:114314. doi: 10.1016/j.expneurol.2022.114314. Epub 2022 Dec 28.
Functional reconstruction after peripheral nerve injury depends on the ability of the regenerated sensory and motor axons to re-innervate the suitable target organs. Therefore, it is essential to explore the cellular mechanisms of peripheral nerve-specific regeneration. In a previous study, we found that sensory and motor fibroblasts can guide Schwann cells to migrate towards the same phenotype. In the present paper, we analyzed the different effects of sensory and motor fibroblasts on sensory or motor neurons. The fibroblasts and neurons co-culture assay showed that compared with motor fibroblasts, sensory fibroblasts promote the neurite outgrowth of sensory neurons on a larger scale, and vice versa. Furthermore, a higher proportion of sensory or motor fibroblasts migrated towards their respective (sensory or motor) neurons. Meanwhile, a comparative proteomic approach was applied to obtain the protein expression profiles of sensory and motor fibroblasts. Among a total of 2597 overlapping proteins identified, we counted 148 differentially expressed items, of those 116 had a significantly higher expression in sensory fibroblasts, and 32 had a significantly greater expression in motor fibroblasts. Functional categorization revealed that differentially expressed proteins were involved in regeneration, axon guidance and cytoskeleton organization, all of which might play a critical role in peripheral nerve-specific regeneration. After nerve crush injury, ITB1 protein expression decreased significantly in motor nerves and increased in sensory nerves. In vitro, ITB1 significantly promoted axonal regeneration of sensory neurons, but had no significant effect on motor neurons. Overall, sensory and motor fibroblasts express different proteins and exert different growth promoting effects on sensory and motor neurons. This comparative proteomic database of sensory and motor fibroblasts could provide future directions for in-depth research on peripheral nerve-specific regeneration. Data are available via ProteomeXchange with identifier PXD034827.
周围神经损伤后的功能重建取决于再生的感觉和运动轴突重新支配合适靶器官的能力。因此，探索周围神经特异性再生的细胞机制至关重要。在先前的一项研究中，我们发现感觉和成肌纤维细胞可引导施万细胞向相同表型迁移。在本文中，我们分析了感觉和成肌纤维细胞对感觉或运动神经元的不同影响。成纤维细胞与神经元共培养试验表明，与成肌纤维细胞相比，感觉成纤维细胞能更大程度地促进感觉神经元的轴突生长，反之亦然。此外，更高比例的感觉或成肌纤维细胞向各自的（感觉或运动）神经元迁移。同时，应用比较蛋白质组学方法获得感觉和成肌纤维细胞的蛋白质表达谱。在总共鉴定出的2597种重叠蛋白中，我们统计出148个差异表达项，其中116个在感觉成纤维细胞中表达显著更高，32个在成肌纤维细胞中表达显著更高。功能分类显示，差异表达蛋白参与再生、轴突导向和细胞骨架组织，所有这些可能在周围神经特异性再生中起关键作用。神经挤压损伤后，ITB1蛋白表达在运动神经中显著降低，在感觉神经中升高。在体外，ITB1显著促进感觉神经元的轴突再生，但对运动神经元无显著影响。总体而言，感觉和成肌纤维细胞表达不同的蛋白质，并对感觉和运动神经元发挥不同的促生长作用。这个感觉和成肌纤维细胞的比较蛋白质组学数据库可为周围神经特异性再生的深入研究提供未来方向。数据可通过ProteomeXchange获得，标识符为PXD034827。
