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Effects of ADSC-Derived Exosome LRRC75A-AS1 on Anti-inflammatory Function After SCI

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Abstract

Spinal cord injury (SCI) is a highly debilitating disorder of the central nervous system that can severely impact an affected patient’s quality of life. This study aimed to examine how adipose-derived mesenchymal stem cell exosomes (ADSC-exos) can be used to treat spinal cord injury. We analysed differentially expressed mRNAs in SCI using bioinformatics data, gene expression profiles in inflammatory cell models, RT-qPCR and WB. Apoptosis was detected with flow cytometry. Starbase provides the control mechanism for FDFT1. Target interactions were detected with dual-luciferase reporter and RIP assays. Exosomes were isolated from adipose tissue-derived mesenchymal stem cells and subsequently characterized with western blot analysis, transmission electron microscopy and nanoparticle tracking analysis. By analysing the GSE102964 database, we found that FDFT1 was significantly downregulated as SCI progressed. Overexpression of FDFT1 can significantly reverse the inflammatory response and apoptosis of BV2 cells induced by hemin. Mechanically, ADSC-exos can affect the expression of FDFT1 through the ceRNA mechanism mediated by LRRC75A-AS1 and in an RBP-dependent manner mediated by IGF2BP2. The overexpression of LRRC75A-AS1 significantly enhances BV2 apoptosis and can be reversed by FDFT1 knockdown. ADSC-exos LRRC75A-AS1 inhibits inflammation and reduces SCI by increasing the expression and stability of FDFT1 mRNA in a ceRNA and RBP-dependent manner.

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Data Availability

The datasets used and/or analysed in the current study are available.

Abbreviations

SCI:

Spinal cord injury

FDFT1:

Farnesyl-diphosphate farnesyltransferase 1

ADSCs:

Adipose mesenchymal stem cells

CNS:

The central nervous system

MSCs:

Mesenchymal stem cells

DEGs:

Differentially expressed genes

GEO:

Gene Expression Omnibus

PPI:

Protein-protein interaction

GO:

Gene Ontology

NTA:

Nanoparticle tracking analysis

NO:

Nitric oxide

TEM:

Transmission electron microscope

ADSC-exos:

Adipose-derived mesenchymal stem cell exosomes

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Funding

This work was financially supported by the National Natural Science Foundation of China (grant number 81701159), the Taishan Scholar Project of Shandong Province of China (grant number tsqn202103200), Shandong Natural Science Foundation General Project (grant number ZR2021MH303) and the Youth Scientific Research Fund of Liaocheng People’s Hospital (grant number 201910915).

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  1. Xiaohui Xing, Peng Xu and Xiaoyang Xing contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Liaocheng People’s Hospital, No. 67 Dongchang West Road, Liaocheng, 252000, China

    Xiaohui Xing, Peng Xu, Zhentao Xu, Zhen Huang, Zhongchen Li, Xueyuan Li & Yilei Xiao

  2. Department of Laboratory, Liaocheng Maternal and Child Health Care Hospital, No.56, Changjiang Road, Liaocheng, 252000, Shandong, China

    Xiaoyang Xing

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  1. Xiaohui Xing
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Contributions

Conceptualization: XhX. Data curation and formal analysis: PX. Investigation: XyX. Methodology: ZX and ZL. Project administration and resources: ZH. Supervision: XL and YX. Writing—original draft: XyX, XhX and Peng Xu. Writing—review and editing: XL and YX.

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Correspondence to Xueyuan Li or Yilei Xiao.

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Animal experiments were conducted according to the Chinese Animal Welfare Act and Guidance for Animal Experimentation of Liaocheng People’s Hospital. The study protocol was approved by the Ethics Committee of the Liaocheng People’s Hospital (Protocol No.: 2021076).

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Xing, X., Xu, P., Xing, X. et al. Effects of ADSC-Derived Exosome LRRC75A-AS1 on Anti-inflammatory Function After SCI. Appl Biochem Biotechnol (2024). https://doi.org/10.1007/s12010-023-04836-9

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