Identification of Spinal Cord MicroRNA and Gene Signatures in a Model of Chronic Stress-Induced Visceral Hyperalgesia in Rat
作者： Sylvie Bradesi , Iordanes Karagiannides , Kyriaki Bakirtzi , Swapna Mahurkar Joshi , Georgios Koukos
DOI: 10.1371/JOURNAL.PONE.0130938
关键词: microRNA 、 DNA microarray 、 STAT protein 、 Cell biology 、 Biology 、 STAT3 、 Gene expression profiling 、 Regulation of gene expression 、 Molecular biology 、 Chronic stress 、 Gene expression
摘要: Author(s): Bradesi, Sylvie; Karagiannides, Iordanes; Bakirtzi, Kyriaki; Joshi, Swapna Mahurkar; Koukos, Georgios; Iliopoulos, Dimitrios; Pothoulakis, Charalabos; Mayer, Emeran A | Abstract: IntroductionAnimal studies have shown that stress could induce epigenetic and transcriptomic alterations essential in determining the balance between adaptive or maladaptive responses to stress. We tested hypothesis chronic rats deregulates coding non-coding gene expression spinal cord, which may underline neuroinflammation nociceptive changes previously observed this model.MethodsMale Wistar were exposed daily handled, for 10 days. At day 11, lumbar segments collected processed mRNA/miRNA isolation followed by profiling using Agilent SurePrint Rat Exon miRNA Microarray platforms. Differentially expressed lists generated dChip program. Microarrays analyzed Ingenuity Pathways Analysis (IPA) tool from Systems. Multiple methods used analysis of miRNA-mRNA functional modules. Quantitative real time RT-PCR Interleukin 6 signal transducer (gp130), Signal Transducer And Activator Of Transcription 3 (STAT3), glial fibrillary acidic protein mir-17-5p performed confirm levels expression.ResultsGene network revealed deregulated different inflammatory (IL-6, JAK/STAT, TNF) metabolic (PI3K/AKT) signaling pathways. MicroRNA array a signature 39 microRNAs stressed rats. MicroRNA-gene showed are regulators two networks relevant processes. Specifically, our modules identified miR-17-5p as an important regulator model. verified increased qPCR situ hybridization. In addition, we gp130 STAT3 (involved intracellular cascades response activation), both predicted targets miR-17-5p. modulatory role mir17-5p modulation visceral sensitivity was confirmed vivo.ConclusionUsing integrative high throughput approach, findings suggest link gp130/STAT3 activation providing new insight into possible mechanisms mediating effect on cord.
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