Integrated bioinformatics analysis identifies the effects of Sema3A/NRP1 signaling in oligodendrocytes after spinal cord injury in rats

Rong Hu; Mengting Shi; Haipeng Xu; Xingying Wu; Kelin He; Yi Chen; Lei Wu; Ruijie Ma

doi:10.7717/peerj.13856

Integrated bioinformatics analysis identifies the effects of Sema3A/NRP1 signaling in oligodendrocytes after spinal cord injury in rats

PeerJ. 2022 Aug 16:10:e13856. doi: 10.7717/peerj.13856. eCollection 2022.

Authors

Rong Hu^#¹, Mengting Shi^#¹, Haipeng Xu¹, Xingying Wu¹, Kelin He^{1

2}, Yi Chen¹, Lei Wu², Ruijie Ma^{1

2}

Affiliations

¹ Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Third School of Clinical Medicine (School of Rehabilitation Medicine), HangZhou, China.
² Department of Acupuncture and Moxibustion, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), HangZhou, China.

^# Contributed equally.

Abstract

Objective: To investigate the effect of Sema3A/NRP1 signaling in oligodendrocytes (OLs) after spinal cord injury.

Methods: Three analysis strategies, namely differential expression gene analysis, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were applied. The protein-protein interaction (PPI) network was constructed using the STRING website to explore the correlation between Sema3A/NRP1 and oligodendrocytes. Then, the T10 spinal cord segment of rats was injured by the Allen method to establish a spinal cord injury (SCI) model. Real-time quantitative PCR, Western blotting, Nissl staining and immunofluorescence staining were used to detect the effect of Sema3A/NRP1 signaling on oligodendrocytes in vivo.

Results: After the SCI model was established, significantly fewer oligodendrocytes were observed. At the same time, R software was used to analyze the expression of related genes, and NRP1 expression was increased. PCR also demonstrated similar results, and NRP1 ligand Sema3A was also upregulated. KEGG and GO functional enrichment analysis indicated that the SCI model was mainly related to cytokine interaction, cell proliferation, differentiation and maturation. Interestingly, we found that NRP1 was involved in semaphorin-plexin signaling pathway neuronal projection guidance and axon guidance, mediating cell growth and migration. Moreover, Sema3A/NRP1 signaling was closely associated with platelet-derived growth factor receptor α (PDGFRα) in the PPI network. When Sema3A/NRP1 signaling was specifically blocked at early stages, PDGFRα expression was effectively inhibited, and the expression of OLs was promoted. Furthermore, inhibition of Sema3A/NRP1 signaling increased the Basso-Beattie-Bresnahan (BBB) score of lower limb motor function in SCI rats and promoted the survival of motor neurons in the ventral horn of the injured spinal cord.

Conclusion: Our data suggest that Sema3A/NRP1 signaling may regulate the development of OPCs and OLs after SCI, thereby affecting functional recovery.

Keywords: Bioinformatic analysis; Oligodendrocyte; PDGFRα; Sema3A/NRP1signal; Spinal cord injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Computational Biology
Oligodendroglia / metabolism
Rats
Receptor, Platelet-Derived Growth Factor alpha / metabolism
Semaphorin-3A* / genetics
Signal Transduction / genetics
Spinal Cord Injuries* / genetics

Substances

Semaphorin-3A
Receptor, Platelet-Derived Growth Factor alpha

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 82174487); Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents; Zhejiang Chinese Medical University Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.