Open AccessAnalysis of Crucial Genes and Pathways Associated with Spared Nerve Injury-Induced Neuropathic Pain
Author(s) -
Dong Mao,
Huang Zhai,
Gang Zhao,
Jingyi Mi,
Yongjun Rui
Publication year - 2020
Publication title -
neural plasticity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.288
H-Index - 68
eISSN - 2090-5904
pISSN - 1687-5443
DOI - 10.1155/2020/8822001
Subject(s) - atf3 , sni , fgf9 , microarray analysis techniques , neuregulin 1 , activating transcription factor , microarray , biology , transcription factor , nerve injury , gene , gene expression , neuroscience , genetics , promoter , biochemistry , hydrolysis , acid hydrolysis
Purpose. The study was aimed at elucidating the molecular mechanism underlying neuropathic pain induced by spared nerve injury (SNI). Methods. The microarray data of GSE30691 were downloaded from the Gene Expression Omnibus database, including sciatic nerve lesion samples at 3, 7, 21, and 40 days after SNI and sham control samples at 3, 7, and 21 days. Differential analysis along with Mfuzz clustering analysis was performed to screen crucial clusters and cluster genes. Subsequently, comprehensive bioinformatic analyses were performed, including functional enrichment analysis, protein-protein interaction (PPI) network and module analysis, and transcription factor- (TF-) gene and miRNA-target interaction predictions. Moreover, the screened differentially expressed genes (DEGs) were corroborated using two other microarray datasets. Results. Three clusters with different change trends over time after SNI were obtained. Protein kinase CAMP-activated catalytic subunit beta (Prkacb), complement C3 (C3), and activating transcription factor 3 (Atf3) were hub nodes in the PPI network, and fibroblast growth factor 9 (Fgf9) was found to interact with more TFs. Prkacb and Fgf9 were significantly enriched in the MAPK signaling pathway. Moreover, rno-miR-3583-5p was targeted by Fgf9, and rno-miR-1912-3p was targeted by neuregulin 1 (Nrg1). Key genes like Nrg1 and Fgf9 in cluster 1, Timp1 in cluster 2, and Atf3 and C3 in cluster 3 were screened out after corroborating microarray data with other microarray data. Conclusions. Key pathways like the MAPK signaling pathway and crucial genes like Prkacb, Nrg1, Fgf9, Timp1, C3, and Atf3 may contribute to SNI-induced neuropathic pain development in rats.