移植
上皮-间质转换
周围神经损伤
间充质干细胞
体内
生物
转化生长因子
雪旺细胞
神经损伤
癌症研究
神经科学
病理
细胞生物学
医学
下调和上调
再生(生物学)
内科学
生物化学
生物技术
基因
作者
Zhaoyang Wu,Haiqi Ding,Yang Chen,Chen‐Bin Huang,Xiaoqing Chen,Hongbo Hu,Yongfa Chen,Wenming Zhang,Xinyu Fang
标识
DOI:10.1016/j.expneurol.2022.114272
摘要
A novel understanding of peripheral nerve injury is epithelial-mesenchymal transition (EMT), which characterizes the process of dedifferentiation and transformation of Schwann cells after nerve injury. Despite being regarded as an important mechanism for healing nerve injuries, long-term EMT is the primary cause of fibrosis in other tissue organs. The potential mechanism promoting neurofibrosis in the process of chronic degeneration of nerve injury and the effects of motor neurons (MNs) transplantation on neurofibrosis and repair of nerve injury were studied by transcriptome sequencing and bioinformatics analysis, which were confirmed by in vivo and in vitro experiments. Even 3 months after nerve injury, the distal nerve maintained high levels of transforming growth factor β-1 (TGFβ-1) and Snail family transcriptional repressor 2 (Snai2). The microenvironment TGFβ-1, Snai2 and endogenous TGFβ-1 formed a positive feedback loop in vivo and in vitro, which may contribute to the sustained EMT state and neurofibrogenesis in the distal injured nerve. Inhibiting TGFβ-1 and Snai2 expression and reversing EMT can be achieved by transferring MNs to distal nerves, and the removal of transplanted MNs is capable of reactivating EMT and promoting the growth of proximal axons. In conclusion, EMT persisting can be an explanation for distal neurofibrosis and a potential therapeutic target. By reversibly regulating EMT, MNs transplantation can alleviate neurofibrogenesis of distal nerve in chronic degeneration.
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