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施万细胞衍生的外泌体通过 Rho/ROCK 通路降低 CSPGs 上 PTP-σ 的激活,从而促进脊髓损伤后的轴突生长。

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

机构信息

Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.

International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin, China.

出版信息

Neurochem Res. 2024 Aug;49(8):2120-2130. doi: 10.1007/s11064-024-04166-0. Epub 2024 May 31.


DOI:10.1007/s11064-024-04166-0
PMID:38819695
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.

摘要

脊髓损伤 (SCI) 是一种严重的神经系统疾病,涉及一个漫长的病理过程。这个过程导致反应性神经胶质细胞上调软骨素硫酸盐蛋白聚糖 (CSPGs),从而阻碍脊髓的修复和再生。CSPG 特异性受体蛋白酪氨酸磷酸酶-西格玛 (PTP-σ) 在 SCI 后的作用在很大程度上仍未被探索。外泌体由于能够轻易地穿过血脑屏障,在 SCI 的诊断、预后和治疗方面具有巨大的潜力。雪旺细胞衍生的外泌体 (SCDEs) 通过减少 CSPG 沉积促进 SCI 后小鼠的功能恢复。然而,SCI 后 SCDEs 减少 CSPGs 的机制尚不清楚。在此,我们观察到在体内 SCI 后神经胶质瘢痕形成过程中 PTP-σ 水平升高和 CSPG 沉积增加。在 SCI 小鼠中注射 SCDEs 后,损伤部位瘢痕组织中的 CSPG 沉积减少,损伤部位周围轴突生长过程中 PTP-σ 的表达增加,运动功能随后恢复。此外,我们还证明了同时使用 Rho/ROCK 抑制剂和 SCDEs 抑制了 SCDEs 对 SCI 后瘢痕组织的修复作用。总之,我们的研究表明,针对 Rho/ROCK 信号通路的 SCDE 治疗可减少 SCI 后 CSPG 中的 PTP-σ 激活,从而抑制瘢痕组织形成。

相似文献

[1]
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. 2024-8

[2]
Increasing toll-like receptor 2 on astrocytes induced by Schwann cell-derived exosomes promotes recovery by inhibiting CSPGs deposition after spinal cord injury.

J Neuroinflammation. 2021-8-9

[3]
Perturbing chondroitin sulfate proteoglycan signaling through LAR and PTPσ receptors promotes a beneficial inflammatory response following spinal cord injury.

J Neuroinflammation. 2018-3-20

[4]
Chondroitin Sulfate Proteoglycans Negatively Modulate Spinal Cord Neural Precursor Cells by Signaling Through LAR and RPTPσ and Modulation of the Rho/ROCK Pathway.

Stem Cells. 2015-5-12

[5]
LAR and PTPσ receptors are negative regulators of oligodendrogenesis and oligodendrocyte integrity in spinal cord injury.

Glia. 2018-11-5

[6]
Chondroitin sulfate proteoglycans inhibit oligodendrocyte myelination through PTPσ.

Exp Neurol. 2013-4-12

[7]
Suppressing CSPG/LAR/PTPσ Axis Facilitates Neuronal Replacement and Synaptogenesis by Human Neural Precursor Grafts and Improves Recovery after Spinal Cord Injury.

J Neurosci. 2022-4-13

[8]
Autophagy induced by Schwann cell-derived exosomes promotes recovery after spinal cord injury in rats.

Biotechnol Lett. 2022-1

[9]
Modulation of Receptor Protein Tyrosine Phosphatase Sigma Increases Chondroitin Sulfate Proteoglycan Degradation through Cathepsin B Secretion to Enhance Axon Outgrowth.

J Neurosci. 2018-5-14

[10]
Molecular mechanisms of scar-sourced axon growth inhibitors.

Brain Res. 2015-9-4

引用本文的文献

[1]
Exosomes-Based Nanotherapeutic Strategies: An Important Approach for Spinal Cord Injury Repair.

Int J Nanomedicine. 2025-8-27

[2]
Extracellular vesicles derived from Schwann cells to enhance bone and dental tissue regeneration: a literature review.

J Nanobiotechnology. 2025-7-11

[3]
Schwann Cells and Their Exosomes: Research Progress and Prospect in Spinal Cord Injury.

Neural Plast. 2025-6-12

[4]
Advanced Therapeutic Approaches Based on Small Extracellular Vehicles (sEVs) For the Regeneration of Spinal Cord Injuries.

Int J Nanomedicine. 2025-6-12

[5]
Exosomes: a promising microenvironment modulator for spinal cord injury treatment.

Int J Biol Sci. 2025-6-5

[6]
The Yin and Yang of Microglia-Derived Extracellular Vesicles in CNS Injury and Diseases.

Cells. 2024-11-6

[7]
Schwann cell-derived exosomes ameliorate peripheral neuropathy induced by ablation of dicer in Schwann cells.

Front Cell Neurosci. 2024-9-2

本文引用的文献

[1]
Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy.

Stem Cell Res Ther. 2024-1-2

[2]
Schwann Cell-Derived Exosomes and Methylprednisolone Composite Patch for Spinal Cord Injury Repair.

ACS Nano. 2023-11-28

[3]
Recovery of Forearm and Fine Digit Function After Chronic Spinal Cord Injury by Simultaneous Blockade of Inhibitory Matrix Chondroitin Sulfate Proteoglycan Production and the Receptor PTPσ.

J Neurotrauma. 2023-12

[4]
Microenvironmental modulation in tandem with human stem cell transplantation enhances functional recovery after chronic complete spinal cord injury.

Biomaterials. 2023-4

[5]
Schwann cell-derived exosomes containing MFG-E8 modify macrophage/microglial polarization for attenuating inflammation via the SOCS3/STAT3 pathway after spinal cord injury.

Cell Death Dis. 2023-1-30

[6]
Immune response following traumatic spinal cord injury: Pathophysiology and therapies.

Front Immunol. 2022

[7]
Generation of neural organoids for spinal-cord regeneration via the direct reprogramming of human astrocytes.

Nat Biomed Eng. 2023-3

[8]
Porcine spinal cord injury model for translational research across multiple functional systems.

Exp Neurol. 2023-1

[9]
Rho Kinase Inhibitor Y27632 Improves Recovery After Spinal Cord Injury by Shifting Astrocyte Phenotype and Morphology via the ROCK/NF-κB/C3 Pathway.

Neurochem Res. 2022-12

[10]
Spinal Cord Injury: The Global Incidence, Prevalence, and Disability From the Global Burden of Disease Study 2019.

Spine (Phila Pa 1976). 2022-11-1

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