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Schwann Cell-Derived Exosomes Induced Axon Growth after Spinal Cord Injury by Decreasing PTP-σ Activation on CSPGs via the Rho/ROCK Pathway

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Abstract

Spinal cord injury (SCI) is a severe neurological condition that involves a lengthy pathological process. This process leads to the upregulation of chondroitin sulfate proteoglycans (CSPGs) by reactive glia, which impedes repair and regeneration in the spinal cord. The role of the CSPG-specific receptor protein tyrosine phosphatase-sigma (PTP-σ) in post-SCI remains largely unexplored. Exosomes have great potential in the diagnosis, prognosis, and treatment of SCI due to their ability to easily cross the blood‒brain barrier. Schwann cell-derived exosomes (SCDEs) promote functional recovery in mice post-SCI by decreasing CSPG deposition. However, the mechanism by which SCDEs decrease CSPGs after SCI remains unknown. Herein, we observed elevated levels of PTP-σ and increased CSPG deposition during glial scar formation after SCI in vivo. After SCDEs were injected into SCI mice, CSPG deposition decreased in scar tissue at the injury site, the expression of PTP-σ increased during axonal growth around the injury site, and motor function subsequently recovered. Additionally, we demonstrated that the use of both Rho/ROCK inhibitors and SCDEs inhibited the reparative effects of SCDEs on scar tissue after SCI. In conclusion, our study revealed that treatment with SCDEs targeting the Rho/ROCK signaling pathway reduced PTP-σ activation in the CSPG post-SCI, which inhibited scar tissue formation.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China [grant numbers 82272470, 82072439]; the Tian** Health Key Discipline Special Project [grant number TJWJ2022XK011]; and the Outstanding Youth Foundation of Tian** Medical University General Hospital [grant number 22ZYYJQ01].

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Author notes

  1. Shibo Zhu, Hongpeng Ma and Mengfan Hou contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Orthopedics, Tian** Medical University General Hospital, Tian**, China

    Shibo Zhu, Hongpeng Ma, Mengfan Hou, Hailiang Li & Guangzhi Ning

  2. International Science and Technology Cooperation Base of Spinal Cord Injury, Tian**, China

    Shibo Zhu, Hongpeng Ma, Mengfan Hou, Hailiang Li & Guangzhi Ning

  3. Tian** Key Laboratory of Spine and Spinal Cord Injury, Tian**, China

    Shibo Zhu, Hongpeng Ma, Mengfan Hou, Hailiang Li & Guangzhi Ning

  4. Department of Orthopedics, Tian** Hospital of ITCWM Nankai Hospital, Tian**, China

    Hailiang Li

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Contributions

GZN conceived and designed the research. HPM and SBZ supervised the project. HPM, SBZ and MFH conducted most experimental work. SBZ performed data analysis. HPM and SBZ wrote the manuscript. GZN reviewed and edited the manuscript.

Corresponding author

Correspondence to Guangzhi Ning.

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Ethical Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tian** Medical University General Hospital (approval number: IRB2023-DW-88).

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The authors declare no competing interests.

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Zhu, S., Ma, H., Hou, M. et al. Schwann Cell-Derived Exosomes Induced Axon Growth after Spinal Cord Injury by Decreasing PTP-σ Activation on CSPGs via the Rho/ROCK Pathway. Neurochem Res 49, 2120–2130 (2024). https://doi.org/10.1007/s11064-024-04166-0

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