PMID- 35990904 OWN - NLM STAT- MEDLINE DCOM- 20230117 LR - 20230117 IS - 2167-8359 (Print) IS - 2167-8359 (Electronic) IS - 2167-8359 (Linking) VI - 10 DP - 2022 TI - Integrated bioinformatics analysis identifies the effects of Sema3A/NRP1 signaling in oligodendrocytes after spinal cord injury in rats. PG - e13856 LID - 10.7717/peerj.13856 [doi] LID - e13856 AB - 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 alpha (PDGFRalpha) in the PPI network. When Sema3A/NRP1 signaling was specifically blocked at early stages, PDGFRalpha 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. CI - (c)2022 Hu et al. FAU - Hu, Rong AU - Hu R AD - Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Third School of Clinical Medicine (School of Rehabilitation Medicine), HangZhou, China. FAU - Shi, Mengting AU - Shi M AD - Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Third School of Clinical Medicine (School of Rehabilitation Medicine), HangZhou, China. FAU - Xu, Haipeng AU - Xu H AD - Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Third School of Clinical Medicine (School of Rehabilitation Medicine), HangZhou, China. FAU - Wu, Xingying AU - Wu X AD - Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Third School of Clinical Medicine (School of Rehabilitation Medicine), HangZhou, China. FAU - He, Kelin AU - He K AD - Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Third School of Clinical Medicine (School of Rehabilitation Medicine), HangZhou, China. AD - Department of Acupuncture and Moxibustion, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), HangZhou, China. FAU - Chen, Yi AU - Chen Y AD - Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Third School of Clinical Medicine (School of Rehabilitation Medicine), HangZhou, China. FAU - Wu, Lei AU - Wu L AD - Department of Acupuncture and Moxibustion, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), HangZhou, China. FAU - Ma, Ruijie AU - Ma R AD - Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Third School of Clinical Medicine (School of Rehabilitation Medicine), HangZhou, China. AD - Department of Acupuncture and Moxibustion, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), HangZhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220816 PL - United States TA - PeerJ JT - PeerJ JID - 101603425 RN - 0 (Semaphorin-3A) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha) MH - Rats MH - Animals MH - *Semaphorin-3A/genetics MH - Receptor, Platelet-Derived Growth Factor alpha/metabolism MH - *Spinal Cord Injuries/genetics MH - Signal Transduction/genetics MH - Oligodendroglia/metabolism MH - Computational Biology PMC - PMC9390322 OTO - NOTNLM OT - Bioinformatic analysis OT - Oligodendrocyte OT - PDGFRalpha OT - Sema3A/NRP1signal OT - Spinal cord injury COIS- The authors declare there are no competing interests. EDAT- 2022/08/23 06:00 MHDA- 2022/08/23 06:01 PMCR- 2022/08/16 CRDT- 2022/08/22 04:03 PHST- 2022/03/10 00:00 [received] PHST- 2022/07/16 00:00 [accepted] PHST- 2022/08/22 04:03 [entrez] PHST- 2022/08/23 06:00 [pubmed] PHST- 2022/08/23 06:01 [medline] PHST- 2022/08/16 00:00 [pmc-release] AID - 13856 [pii] AID - 10.7717/peerj.13856 [doi] PST - epublish SO - PeerJ. 2022 Aug 16;10:e13856. doi: 10.7717/peerj.13856. eCollection 2022.