Fang Zhou, Zou Jian-Long
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
Key Laboratory of Neurological Function and Health, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
Front Cell Neurosci. 2021 Dec 23;15:816781. doi: 10.3389/fncel.2021.816781. eCollection 2021.
Collagen VI (COL6) in the microenvironment was recently identified as an extracellular signal that bears the function of promoting orderly axon bundle formation. However, the large molecular weight of COL6 (≈2,000 kDa) limits its production and clinical application. It remains unclear whether the smaller subunit α chains of COL6 can exert axon bundling and ordering effects independently. Herein, based on a dorsal root ganglion (DRG) model, the contributions of three main COL6 α chains on orderly nerve bundle formation were analyzed, and COL6 α2 showed the largest contribution weight. A recombinant COL6 α2 chain was produced and demonstrated to promote the formation of orderly axon bundles through the NCAM1-mediated pathway. The addition of COL6 α2 in conventional hydrogel triggered orderly nerve regeneration in a rat sciatic nerve defect model. Immunogenicity assessment showed weaker immunogenicity of COL6 α2 compared to that of the COL6 complex. These findings suggest that recombinant COL6 α2 is a promising material for orderly nerve regeneration.
微环境中的胶原蛋白VI（COL6）最近被确定为一种细胞外信号，具有促进轴突束有序形成的功能。然而，COL6的大分子质量（约2000 kDa）限制了其生产和临床应用。目前尚不清楚COL6的较小亚基α链是否能独立发挥轴突成束和有序排列的作用。在此，基于背根神经节（DRG）模型，分析了COL6的三条主要α链对神经束有序形成的贡献，其中COL6 α2的贡献权重最大。制备了重组COL6 α2链，并证明其通过NCAM1介导的途径促进轴突束的有序形成。在传统水凝胶中添加COL6 α2可在大鼠坐骨神经缺损模型中引发神经的有序再生。免疫原性评估显示，与COL6复合物相比，COL6 α2的免疫原性较弱。这些发现表明，重组COL6 α2是一种有前景的用于神经有序再生的材料。
Zotero 插件
