Tang Leili, Zhang Min, Liu Xingyu, Zhu Ye, Chen Xin, Zhong Jingfei, Li Meiyuan
Key Laboratory of Neuroregeneration of Jiangsu, Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
School of Medicine, Nantong University, Nantong, China.
Ann Transl Med. 2021 Oct;9(20):1581. doi: 10.21037/atm-21-5181.
polypeptide k (ABPPk) is an active ingredient separated from the polypeptides (ABPP) in traditional Chinese medicine. In the present study, we investigated the promoting effects and molecular mechanisms of ABPPk on the proliferation of Schwann cells (SCs).
Primary SCs were cultured with ABPPk or nerve growth factor (NGF) , and cell viability, cell cycle, EdU assay, and the expressions of proliferating cell nuclear antigen (PCNA) and Ki67 were analyzed. In addition, RNA-seq was used for bioinformatics analysis at different time points. PCNA was detected at different time points in a rat sciatic nerve injury model to further determining the role of ABPPk in sciatic nerve injury repair.
We found that ABPPk could effectively promote the proliferation of SCs, while ABPPk and NGF had different molecular mechanisms for their proliferation at different time points. Weighted gene co-expression network analysis (WGCNA) showed that ABPPk was mainly involved in the positive regulation of cell proliferation and epigenetic regulation of cell proliferation, while the main cell proliferation-related modules that NGF participated in were attenuation of negative regulation of cell proliferation and positive regulation of cell cycle. There were significant differences in the genes involved in different modules between the two groups, and ABPPk differed from NGF in the biological process of SC migration, differentiation, movement, and development in terms of action time and key genes. Functional enrichment analysis revealed ABPPk had more advantages and participation in the axon extension and vascular system areas. Furthermore, ABPPk significantly promoted the proliferation of SCs .
Through and studies, we identified the promoting effects of ABPPk on the proliferation of SCs. Using high-throughput sequencing technology, our work more comprehensively revealed the characteristics and mechanism of ABPPk on SCs. These results further enrich an understanding of the positive function and molecular mechanism of ABPPk in peripheral nerve regeneration and are conducive to the discovery of new therapeutic targets for peripheral nerve regeneration.
多肽k（ABPPk）是从中药多肽（ABPP）中分离出的一种活性成分。在本研究中，我们探讨了ABPPk对雪旺细胞（SCs）增殖的促进作用及其分子机制。
将原代SCs与ABPPk或神经生长因子（NGF）一起培养，并分析细胞活力、细胞周期、EdU检测以及增殖细胞核抗原（PCNA）和Ki67的表达。此外，在不同时间点使用RNA测序进行生物信息学分析。在大鼠坐骨神经损伤模型的不同时间点检测PCNA，以进一步确定ABPPk在坐骨神经损伤修复中的作用。
我们发现ABPPk能有效促进SCs的增殖，而ABPPk和NGF在不同时间点对SCs增殖的分子机制不同。加权基因共表达网络分析（WGCNA）表明，ABPPk主要参与细胞增殖的正调控和细胞增殖的表观遗传调控，而NGF参与的主要细胞增殖相关模块是细胞增殖负调控的减弱和细胞周期的正调控。两组参与不同模块的基因存在显著差异，ABPPk与NGF在SCs迁移、分化、运动和发育的生物学过程中，在作用时间和关键基因方面有所不同。功能富集分析显示ABPPk在轴突延伸和血管系统区域具有更多优势并参与其中。此外，ABPPk显著促进SCs的增殖。
通过本研究，我们确定了ABPPk对SCs增殖的促进作用。利用高通量测序技术，我们的工作更全面地揭示了ABPPk对SCs的作用特点和机制。这些结果进一步丰富了对ABPPk在周围神经再生中的积极作用和分子机制的认识，有利于发现周围神经再生的新治疗靶点。
