Shen Yinying, Zhu Jun, Liu Qianyan, Ding Shiyan, Dun Xinpeng, He Jianghong
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
Front Cell Neurosci. 2021 Oct 14;15:743532. doi: 10.3389/fncel.2021.743532. eCollection 2021.
CD146 is cell adhesion molecule and is implicated in a variety of physiological and pathological processes. However, the involvement of CD146 in peripheral nerve regeneration has not been studied yet. Here, we examine the spatial and temporal expression pattern of CD146 in injured mouse sciatic nerve via high-throughput data analysis, RT-PCR and immunostaining. By microarray data analysis and RT-PCR validation, we show that CD146 mRNA is significantly up-regulated in the nerve bridge and in the distal nerve stump following mouse sciatic nerve transection injury. By single cell sequencing data analysis and immunostaining, we demonstrate that CD146 is up-regulated in Schwann cells and cells associated with blood vessels following mouse peripheral nerve injury. Bioinformatic analysis revealed that CD146 not only has a key role in promoting of blood vessel regeneration but also regulates cell migration. The biological function of CD146 in Schwann cells was further investigated by knockdown of CD146 in rat primary Schwann cells. Functional assessments showed that knockdown of CD146 decreases viability and proliferation of Schwann cells but increases Schwann cell migration. Collectively, our findings imply that CD146 could be a key cell adhesion molecule that is up-regulated in injured peripheral nerves to regulate peripheral nerve regeneration.
CD146是一种细胞粘附分子,参与多种生理和病理过程。然而,CD146在周围神经再生中的作用尚未得到研究。在此,我们通过高通量数据分析、逆转录-聚合酶链反应(RT-PCR)和免疫染色,研究了CD146在小鼠坐骨神经损伤后的时空表达模式。通过微阵列数据分析和RT-PCR验证,我们发现小鼠坐骨神经横断损伤后,神经桥和远端神经残端中的CD146 mRNA显著上调。通过单细胞测序数据分析和免疫染色,我们证明小鼠周围神经损伤后,雪旺细胞和血管相关细胞中的CD146上调。生物信息学分析表明,CD146不仅在促进血管再生中起关键作用,还调节细胞迁移。通过在大鼠原代雪旺细胞中敲低CD146,进一步研究了CD146在雪旺细胞中的生物学功能。功能评估表明,敲低CD146会降低雪旺细胞的活力和增殖,但会增加雪旺细胞的迁移。总的来说,我们的研究结果表明,CD146可能是一种关键的细胞粘附分子,在损伤的周围神经中上调,以调节周围神经再生。