Motor neurons transplantation alleviates neurofibrogenesis during chronic degeneration by reversibly regulating Schwann cells epithelial-mesenchymal transition

A novel understanding of peripheral nerve injury is epithelial-mesenchymal transition (EMT), which charac-terizes 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 I3-1 (TGFI3-1) and Snail family transcriptional repressor 2 (Snai2). The microenvironment TGFI3-1, Snai2 and endogenous TGFI3-1 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 TGFI3-1 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.

Automated summary

A novel understanding of peripheral nerve injury is the epithelial-mesenchymal transition (EMT), which refers to the dedifferentiation and transformation of Schwann cells after nerve injury. Long-term EMT is the primary cause of fibrosis in tissue organs. A study investigated the potential mechanism of neurofibrosis in chronic degeneration of nerve injury and the effects of motor neurons (MNs) transplantation on neurofibrosis and nerve injury repair. The results showed that even 3 months after nerve injury, the distal nerve maintained high levels of transforming growth factor and transcriptional repressor, which formed a positive feedback loop promoting sustained EMT state and neurofibrogenesis. MNs transplantation inhibited EMT and promoted proximal axon growth, while the removal of transplanted MNs reactivated EMT. In conclusion, EMT can explain distal neurofibrosis and may be a potential therapeutic target. MNs transplantation can alleviate neurofibrogenesis in chronic degeneration by regulating EMT reversibly.