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The transcriptional landscape of dorsal root ganglia after sciatic nerve transection.

ABSTRACT: Following peripheral nerve injury, transcriptional responses are orchestrated to regulate the expression of numerous genes in the lesioned nerve, thus activating the intrinsic regeneration program. To better understand the molecular regulation of peripheral nerve regeneration, we aimed at investigating the transcriptional landscape of dorsal root ganglia (DRGs) after sciatic nerve transection in rats. The cDNA microarray analysis was used to identify thousands of genes that were differentially expressed at different time points post nerve injury (PNI). The results from Euclidean distance matrix, principal component analysis, and hierarchical clustering indicated that 2 nodal transitions in temporal gene expressions could segregate 3 distinct transcriptional phases within the period of 14 d PNI. The 3 phases were designated as "a stress response phase", "a pre-regeneration phase", and "a regeneration phase", respectively, by referring to morphological observation of post-nerve-injury changes. The gene ontology (GO) analysis revealed the distinct features of biological process, cellular component, and molecular function at each transcriptional phase. Moreover, Ingenuity Pathway Analysis suggested that differentially expressed genes, mainly transcription factors and genes associated with neurite/axon growth, might be integrated into regulatory networks to mediate the regulation of peripheral nerve regeneration in a highly cooperative manner.

SUBMITTER: Li S

PROVIDER: S-EPMC4649668 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The transcriptional landscape of dorsal root ganglia after sciatic nerve transection.

Li Shiying S Xue Chengbin C Yuan Ying Y Zhang Ruirui R Wang Yaxian Y Wang Yongjun Y Yu Bin B Liu Jie J Ding Fei F Yang Yuming Y Gu Xiaosong X

Scientific reports 20151118

Following peripheral nerve injury, transcriptional responses are orchestrated to regulate the expression of numerous genes in the lesioned nerve, thus activating the intrinsic regeneration program. To better understand the molecular regulation of peripheral nerve regeneration, we aimed at investigating the transcriptional landscape of dorsal root ganglia (DRGs) after sciatic nerve transection in rats. The cDNA microarray analysis was used to identify thousands of genes that were differentially e ...[more]

PMID: 26576491

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Project description:BackgroundNeuropathic pain (NeP) is a pathological condition arising from a lesion or disease affecting the somatosensory system. Accumulating evidence has shown that circular RNAs (circRNAs) exert critical functions in neurodegenerative diseases by sponging microRNAs (miRNAs). However, the functions and regulatory mechanisms of circRNAs as competitive endogenous RNAs (ceRNAs) in NeP remain to be determined.MethodsThe sequencing dataset GSE96051 was obtained from the public Gene Expression Omnibus (GEO) database. First, we conducted a comparison of gene expression profiles in the L3/L4 dorsal root ganglion (DRG) of sciatic nerve transection (SNT) mice (n = 5) and uninjured mice (Control) (n = 4) to define the differentially expressed genes (DEGs). Then, critical hub genes were screened by exploring protein-protein interaction (PPI) networks with Cytoscape software, and the miRNAs bound to them were predicted and selected and then validated by qRT-PCR. Furthermore, key circRNAs were predicted and filtered, and the network of circRNA-miRNA-mRNA in NeP was constructed.ResultsA total of 421 DEGs were identified, including 332 upregulated genes and 89 downregulated genes. Ten hub genes, including IL6, Jun, Cd44, Timp1, and Csf1, were identified. Two miRNAs, mmu-miR-181a-5p and mmu-miR-223-3p, were preliminarily verified as key regulators of NeP development. In addition, circARHGAP5 and circLPHN3 were identified as key circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these differentially expressed mRNAs and targeting miRNAs were involved in signal transduction, positive regulation of receptor-mediated endocytosis and regulation of neuronal synaptic plasticity. These findings have useful implications for the exploration of new mechanisms and therapeutic targets for NeP.ConclusionThese newly identified miRNAs and circRNAs in networks reveal potential diagnostic or therapeutic targets for NeP.

Dataset Information

The transcriptional landscape of dorsal root ganglia after sciatic nerve transection.

Publications

The transcriptional landscape of dorsal root ganglia after sciatic nerve transection.

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