Recombinant COL6 α2 as a Self-Organization Factor That Triggers Orderly Nerve Regeneration Without Guidance Cues.
Recombinant COL6 α2 as a Self-Organization Factor That Triggers Orderly Nerve Regeneration Without Guidance Cues.
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重组 COL6 α2 作为自组织因子，无需指导即可触发有序神经再生
DOI：
10.3389/fncel.2021.816781
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发表时间：
2021
影响因子：
5.3
通讯作者：
Zou JL
中科院分区：
文献类型：
--
作者：
Fang Z;Zou JL
微环境中的VI型胶原(COL6)是近年来发现的一种细胞外信号，具有促进轴突束有序形成的功能。然而，COL6(≈2,000 kDa)的大分子量限制了其生产和临床应用。目前尚不清楚COL6的较小亚单位α链是否能独立地发挥轴突捆绑和排序作用。在背根节体外模型的基础上，分析了COL6α链对神经束有序形成的贡献，其中COL6α2的贡献率最大。重组的COL6NCAM12链通过α介导的途径促进有序轴突束的形成。在大鼠坐骨神经缺损模型中加入CoL6-α-2可促进神经有序再生。免疫原性评价显示，COL6α2的免疫原性弱于COL6复合体。提示重组COL6-α-2是一种有希望的有序神经再生材料。
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) ex vivo 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.
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