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Constructing and Validating a Network of Potential Olfactory Sheathing Cell Transplants Regulating Spinal Cord Injury Progression

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Abstract

The pathology of spinal cord injury (SCI), including primary and secondary injuries, primarily involves hemorrhage, ischemia, edema, and inflammatory responses. Cell transplantation has been the most promising treatment for SCI in recent years; however, its specific molecular mechanism remains unclear. In this study, bioinformatics analysis verified by experiment was used to elucidate the hub genes associated with SCI and to discover the underlying molecular mechanisms of cell intervention. GSE46988 data were downloaded from the Gene Expression Omnibus dataset. In our study, differentially expressed genes (DEGs) were reanalyzed using the “R” software (R v4.2.1). Functional enrichment and protein–protein interaction network analyses were performed, and key modules and hub genes were identified. Network construction was performed for the hub genes and their associated miRNAs. Finally, a semi-quantitative analysis of hub genes and pathways was performed using quantitative real-time polymerase chain reaction. In total, 718 DEGs were identified, mainly enriched in immune and inflammation-related functions. We found that Cd4, Tp53, Rac2, and Akt3 differed between vehicle and transplanted groups, suggesting that these genes may play an essential role in the transplantation of olfactory ensheathing cells, while a toll-like receptor signaling pathway was significantly enriched in Gene set enrichment analysis, and then, the differences were statistically significant by experimentally verifying the expression of their associated molecules (Tlr4, Nf-κb, Ikkβ, Cxcl2, and Tnf-α). In addition, we searched for upstream regulatory molecules of these four central genes and constructed a regulatory network. This study is the first to construct a regulatory network for olfactory ensheathing cell transplantation in treating SCI, providing a new idea for SCI cell therapy.

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Data Availability

The data used to support the findings of this study have been included in this article.

Abbreviations

SCI:

Spinal cord injury

GSE:

GEO series

DEGs:

Differentially expressed genes

PPI:

Protein–protein interaction network

GSEA:

Gene set enrichment analysis

qRT-PCR:

Quantitative real-time polymerase chain reaction

Tp53:

Tumor suppressor p53

Rac2:

Rac family small GTPase 2

OECs:

Olfactory ensheathing cells

miRNA:

MicroRNA

mRNA:

Messenger RNA

KEGG:

Kyoto Encyclopedia of Genes and Genome

HE:

Hematoxylin and eosin

SEM:

Mean standard error

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Acknowledgements

We acknowledge the GEO databases for providing their platforms and the contributors for uploading meaningful datasets.

Funding

This work was supported by the Science and Technology Bureau of Quanzhou.

(Grant Number 2022C036R), Medical Innovation Science and Technology Project of Fujian Province (Grant Number 2020CXA047), and Natural Science Foundation of Fujian Province (Grant Number 2020J01227).

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Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China

    Yan Zhang, Yu-shen Yang, Wei-can Chen, Cong-mei Wang & He-fan He

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  1. Yan Zhang
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  2. Yu-shen Yang
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  3. Wei-can Chen
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  4. Cong-mei Wang
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Contributions

YZ, YSY, and CMW contributed to the study design and data analysis. YZ wrote the paper. WCC and HFH critically revised the manuscript for its intellectual content.

Corresponding author

Correspondence to He-fan He.

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All animal procedures were performed in accordance with the Care and Use of Laboratory Animals guidelines and were approved by Fujian Medical University.

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Zhang, Y., Yang, Ys., Chen, Wc. et al. Constructing and Validating a Network of Potential Olfactory Sheathing Cell Transplants Regulating Spinal Cord Injury Progression. Mol Neurobiol 60, 6883–6895 (2023). https://doi.org/10.1007/s12035-023-03510-9

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