Exploring the Biomarkers and Potential Mechanisms of Botulinum Toxin Type A in the Treatment of Microglial Inflammatory Activation through P2X7 Receptors based on Transcriptome Sequencing


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Abstract

Aims:This study aims to explore the potential mechanism by which Botulinum toxin type A (BoNT/ A) inhibits microglial inflammatory activation through P2X7 receptors (P2X7R).

Background:BoNT/A is a promising analgesic drug, and previous studies have established that it alleviates Neuropathic Pain (NP) by inhibiting microglial inflammatory activation. This study examined the biomarkers and potential mechanisms by which BoNT/A relieves neuropathic pain by mediating microglial P2X7R and analyzing transcriptome sequencing data from mouse BV-2 microglial cells.

Objective:The P2X7R agonist Bz-ATP was used to induce microglial inflammatory activation, whilst RNAseq technology was used to explore the biomarkers and potential mechanisms through which BoNT/A suppresses microglial inflammation.

Methods:RNA sequencing was performed on three BV-2 cell samples treated with a P2X7R specific activator (Bz-ATP) and three BV-2 cell samples pre-treated with BoNT/A. Only data that successfully passed quality control measures were included in subsequent analysis. Initially, Differentially Expressed Genes (DEGs) were identified from BoNT/A and control samples, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Biomarkers were then identified by constructing a Protein- Protein Interaction (PPI) network and utilizing the CytoHubba plug-in in Cytoscape software. Lastly, enrichment analysis and regulatory network analysis were performed to elucidate the potential mechanism of BoNT/A in the treatment of NP.

Results:93 DEGs related to the "cell component size regulation" GO term and enriched in the "axon guidance" KEGG pathway were identified. Subsequently, 6 biomarkers were identified, namely PTPRF, CHDH, CKM, Ky, Sema3b, and Sema3f, which were enriched in pathways related to biosynthesis and metabolism, disease progression, signal transduction, and organelle function, including the "ribosome" and "Wnt signaling pathway." Finally, a competing endogenous RNA (ceRNAs) network was constructed from 6 mRNAs, 66 miRNAs, and 31 lncRNAs, forming a complex relationship network.

Conclusion:Six genes (PTPRF, Sema3b, Sema3f, CHDH, CKM, and Ky) were identified as biomarkers of microglial inflammatory activation following BoNT/A treatment. This finding may provide a valuable reference for the relief and treatment of neuropathic pain.

About the authors

Kai Zhang

Department of Spine Surgery, Lanzhou University Second Hospital

Email: info@benthamscience.net

Yi Ren

Department of Spine Surgery, Lanzhou University Second Hospital

Email: info@benthamscience.net

Jiayang Lv

Department of Spine Surgery, Lanzhou University Second Hospital

Email: info@benthamscience.net

Peng Mao

Department of Spine Surgery, Lanzhou University Second Hospital

Email: info@benthamscience.net

Wenming Zhou

Department of Spine Surgery, Lanzhou University Second Hospital

Email: info@benthamscience.net

Yongqiang Shi

Department of Spine Surgery, Lanzhou University Second Hospital

Email: info@benthamscience.net

Kaisheng Zhou

Department of Spine Surgery, Lanzhou University Second Hospital

Email: info@benthamscience.net

Linna Wang

Department of Drug Development, Lanzhou Biotechnique Development Co., LTD

Email: info@benthamscience.net

Chengjun Zhang

Department of Drug Development, Lanzhou Biotechnique Development Co., LTD

Email: info@benthamscience.net

Haihong Zhang

Department of Spine Surgery, Lanzhou University Second Hospital

Author for correspondence.
Email: info@benthamscience.net

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