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Exosomes Derived from lncRNA TCTN2-Modified Mesenchymal Stem Cells Improve Spinal Cord Injury by miR-329-3p/IGF1R Axis

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Abstract

Mesenchymal stem cells (MSCs)-derived exosomes play significant roles in alleviating spinal cord injury (SCI). Previous study showed that long non-coding RNA tectonic family member 2 (TCTN2) was able to relieve SCI. Herein, whether TCTN2 exerted its roles in functional recovery after SCI via exosomes derived from MSCs was explored. The SCI model was established in rats, and the neurological function was evaluated using the Basso, Beattie, and Bresnahan (BBB) scoring. Lipopolysaccharide (LPS)-induced differentiated PC12 cells were used as an in vitro model for neurotoxicity research. The expression of genes and proteins was detected by qRT-PCR and Western blot. Exosomes were isolated by ultracentrifugation and qualified by TEM and Western blot. In vitro assays were performed using CCK-8 assay, EdU assay, and flow cytometry, respectively. Dual-luciferase reporter assay and RIP assay were used to confirm the target relationship between miR-329-3p and TCTN2 or insulin-like growth factor1 receptor (IGF1R). TCTN2 expression was down-regulated in SCI model rat and lipopolysaccharide (LPS)-stimulated PC12 cells. MSCs produced exosomes and could package TCTN2 into secreted exosomes. Tail vein injection of TCTN2 exosomes into rats significantly improved functional recovery of SCI. Meanwhile, TCTN2 exosomes treatment alleviated LPS-induced neuronal apoptosis, inflammation, and oxidative stress in vitro. Additionally, TCTN2 targeted miR-329-3p and subsequently regulated the expression of its target IGF1R. Rescue assays suggested that miR-329-3p/IGF1R axis mediated the beneficial effects of TCTN2 exosomes on LPS-treated PC12 cells. In all, exosomes derived from TCTN2-modified MSCs could improve functional recovery of SCI in vivo and attenuate LPS-induced neuronal apoptosis, inflammation, and oxidative stress in vitro via miR-329-3p/IGF1R axis, suggesting a novel insight into the development of MSC-exosomes-based therapy for SCI.

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Data and Materials Availability

The analyzed datasets generated during the present study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Spine Surgery, Hainan General Hospital, Haikou, Hainan, China

    Jian Liu & Mingxia Lin

  2. Jinan University, Guangzhou, China

    Jian Liu

  3. Department of laboratory, The Fifth People Hospital of Hainan Province, No 49, Longkun South Road, Haikou, 570206, Hainan, China

    Feng Qiao

  4. Department of Endoscopy, Jilin Cancer Hospital, Changchun, Jilin, China

    Chenghua Zhang

Authors
  1. Jian Liu
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  2. Mingxia Lin
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  3. Feng Qiao
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  4. Chenghua Zhang
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Contributions

Conceptualization and methodology: Mingxia Lin and Feng Qiao; formal analysis and data curation: Feng Qiao and Chenghua Zhang; validation and investigation: Jian Liu and Feng Qiao; writing-original draft preparation and writing-review and editing: Jian Liu, Mingxia Lin, and Feng Qiao; approval of final manuscript: all authors.

Corresponding author

Correspondence to Feng Qiao.

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Ethics Approval and Consent to Participate

The present study was approved by the ethical review committee of Hainan General Hospital with grant No. 20190628. Written informed consent was obtained from all enrolled patients.

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The authors declare no competing interests.

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Highlight

• TCTN2 is down-regulated in SCI model rat and LPS-stimulated PC12 cells

• MSCs packages TCTN2 into secreted exosomes

• TCTN2 exosomes improve functional recovery after SCI in vivo

• TCTN2 exosomes suppress neuronal apoptosis, inflammation, and oxidative stress in vitro

• TCTN2 exosomes exert its neuroprotective effects via miR-329-3p/IGF1R axis

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Liu, J., Lin, M., Qiao, F. et al. Exosomes Derived from lncRNA TCTN2-Modified Mesenchymal Stem Cells Improve Spinal Cord Injury by miR-329-3p/IGF1R Axis. J Mol Neurosci 72, 482–495 (2022). https://doi.org/10.1007/s12031-021-01914-7

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  • DOI: https://doi.org/10.1007/s12031-021-01914-7

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