Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Exp Physiol. 2023 Apr;108(4):621-635. doi: 10.1113/EP090751. Epub 2023 Feb 28.
What is the central question of this study? Although fibroblasts are involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. What is the main finding and its importance? Nerve-derived fibroblasts have a greater neurite-promoting effect than skin-derived fibroblasts, and epineurium-derived fibroblasts can promote neurite outgrowth more effectively than parenchyma-derived fibroblasts. The epineurium-derived fibroblasts and parenchyma-derived fibroblasts have distinctly different molecular profiles, including genes of soluble factors to promote axonal growth. Fibroblasts are molecularly and functionally different depending on their localization in nerve tissue, and epineurium-derived fibroblasts might be involved in axon regeneration after peripheral nerve injury more than previously thought.
Although fibroblasts (Fb) are components of a peripheral nerve involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. The objective of the present study was to investigate the capacity of Fb derived from peripheral nerves to stimulate the outgrowth of neurites from adult dorsal root ganglion neurons and to clarify their molecular characteristics. Fibroblasts were prepared from the epineurium and parenchyma of rat sciatic nerves and skin. The Fb derived from epineurium showed the greatest effect on neurite outgrowth, followed by the Fb derived from parenchyma, indicating that Fb derived from nerves promote neurite outgrowth more effectively than skin-derived Fb. Although both soluble and cell-surface factors contributed evenly to the neurite-promoting effect of nerve-derived Fb, in crush and transection injury models, Fb were not closely associated with regenerating axons, indicating that only soluble factors from Fb are available to regenerating axons. A transcriptome analysis revealed that the molecular profiles of these Fb were distinctly different and that the gene expression profiles of soluble factors that promote axonal growth are unique to each Fb. These findings indicate that Fb are molecularly and functionally different depending on their localization in nerve tissue and that Fb derived from epineurium might be involved more than was previously thought in axon regeneration after peripheral nerve injury.
本研究的核心问题是什么？虽然成纤维细胞参与了与周围神经损伤相关的再生过程，但关于其特征的详细信息还很缺乏。主要发现及其重要性是什么？神经来源的成纤维细胞比皮肤来源的成纤维细胞具有更强的促进轴突生长的作用，而外膜来源的成纤维细胞比实质来源的成纤维细胞更能有效地促进轴突生长。外膜来源的成纤维细胞和实质来源的成纤维细胞具有明显不同的分子特征，包括促进轴突生长的可溶性因子基因。成纤维细胞因其在神经组织中的定位而在分子和功能上有所不同，外膜来源的成纤维细胞可能比以前认为的更参与周围神经损伤后的轴突再生。
虽然成纤维细胞（Fb）是参与与周围神经损伤相关的再生过程的周围神经的组成部分，但关于其特征的详细信息还很缺乏。本研究的目的是研究源自周围神经的 Fb 刺激成年背根神经节神经元轴突生长的能力，并阐明其分子特征。从大鼠坐骨神经和皮肤的外膜和实质中制备 Fb。外膜来源的 Fb 对轴突生长的促进作用最大，其次是实质来源的 Fb，表明神经来源的 Fb 比皮肤来源的 Fb 更有效地促进轴突生长。虽然可溶性和细胞表面因子对神经来源的 Fb 的促神经突生长作用都有贡献，但在挤压和横断损伤模型中，Fb 与再生轴突没有密切相关，表明只有 Fb 的可溶性因子可用于再生轴突。转录组分析显示，这些 Fb 的分子特征明显不同，促进轴突生长的可溶性因子的基因表达谱是每种 Fb 所特有的。这些发现表明，Fb 因其在神经组织中的定位而在分子和功能上有所不同，外膜来源的 Fb 可能比以前认为的更参与周围神经损伤后的轴突再生。
