Identification of novel gene and pathway targets for human epilepsy treatment

被引:14
作者
Jin, Ying [1 ]
Zhao, Chunzhe [1 ]
Chen, Lihui [1 ]
Liu, Xiangyu [1 ]
Pan, Shuxiao [1 ]
Ju, Dongsheng [1 ]
Ma, Jing [1 ]
Li, Jinying [1 ]
Wei, Bo [2 ]
机构
[1] Jilin Oilfield Gen Hosp, Dept Neurol, Songyuan 131200, Peoples R China
[2] Jilin Univ, Div Neurosurg 2, Dept Neurosurg, China Japan Union Hosp, Changchun 130033, Kagawa, Peoples R China
关键词
Epilepsy; Differentially expressed genes; Functional annotation; Protein-protein interaction network; Co-expression module; MICROARRAY DATA; IMMUNE; INNATE; PHOSPHORYLATION; MECHANISM; GLUTAMATE; CHILDREN; SEIZURES; PROTEIN; MODELS;
D O I
10.1186/s40659-015-0060-5
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: The aim of this study was to explore epilepsy-related mechanism so as to figure out the possible targets for epilepsy treatment. Methods: The gene expression profile dataset GES32534 was downloaded from Gene Expression Omnibus database. We identified the differentially expressed genes (DEGs) by Affy package. Then the DEGs were used to perform gene ontology (GO) and pathway enrichment analyses. Furthermore, a protein-protein interaction (PPI) network was constructed with the DEGs followed by co-expression modules construction and analysis. Results: Total 420 DEGs were screened out, including 214 up-regulated and 206 down-regulated genes. Functional enrichment analysis revealed that down-regulated genes were mainly involved in the process of immunity regulation and biological repairing process while up-regulated genes were closely related to transporter activity. PPI network analysis showed the top ten genes with high degrees were all down-regulated, among which FN1 had the highest degree. The up-regulated and down-regulated DEGs in the PPI network generated two obvious sub-co-expression modules, respectively. In up-co-expression module, SCN3B (sodium channel, voltage gated, type III beta subunit) was enriched in GO: 0006814 similar to sodium ion transport. In down-co-expression module, C1QB (complement C1s), C1S (complement component 1, S subcomponent) and CFI (complement factor I) were enriched in GO: 0006955 similar to immune response. Conclusion: The immune response and complement system play a major role in the pathogenesis of epilepsy. Additionally, C1QB, C1S, CFI, SCN3B and FN1 may be potential therapeutic targets for epilepsy.
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页数:9
相关论文
共 34 条
[1]   Astrocyte immune responses in epilepsy [J].
Aronica, Eleonora ;
Ravizza, Teresa ;
Zurolo, Emanuele ;
Vezzani, Annamaria .
GLIA, 2012, 60 (08) :1258-1268
[2]   Reciprocal Changes in Phosphorylation and Methylation of Mammalian Brain Sodium Channels in Response to Seizures [J].
Baek, Je-Hyun ;
Rubinstein, Moran ;
Scheuer, Todd ;
Trimmer, James S. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (22) :15363-15373
[3]   Epilepsy and driving: Potential impact of transient impaired consciousness [J].
Chen, William C. ;
Chen, Eric Y. ;
Gebre, Rahiwa Z. ;
Johnson, Michelle R. ;
Li, Ningcheng ;
Vitkovskiy, Petr ;
Blumenfeld, Hal .
EPILEPSY & BEHAVIOR, 2014, 30 :50-57
[4]   Cellular injury and neuroinflammation in children with chronic intractable epilepsy [J].
Choi, Jieun ;
Nordli, Douglas R., Jr. ;
Alden, Tord D. ;
DiPatri, Arthur, Jr. ;
Laux, Linda ;
Kelley, Kent ;
Rosenow, Joshua ;
Schuele, Stephan U. ;
Rajaram, Veena ;
Koh, Sookyong .
JOURNAL OF NEUROINFLAMMATION, 2009, 6
[5]   Mechanism of Ion Permeation and Selectivity in a Voltage Gated Sodium Channel [J].
Corry, Ben ;
Thomas, Michael .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2012, 134 (03) :1840-1846
[6]   Astrocytic regulation of glutamate homeostasis in epilepsy [J].
Coulter, Douglas A. ;
Eid, Tore .
GLIA, 2012, 60 (08) :1215-1226
[7]   DAVID: Database for annotation, visualization, and integrated discovery [J].
Dennis, G ;
Sherman, BT ;
Hosack, DA ;
Yang, J ;
Gao, W ;
Lane, HC ;
Lempicki, RA .
GENOME BIOLOGY, 2003, 4 (09)
[8]  
dos Santos Lunardi., 2012, Journal of Epilepsy and Clinical Neurophysiology, V18, P79
[9]   Loss of glutamine synthetase in the human epileptogenic hippocampus:: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy [J].
Eid, T ;
Thomas, MJ ;
Spencer, DD ;
Rundén-Pran, E ;
Lai, JCK ;
Malthankar, GV ;
Kim, JH ;
Danbolt, NC ;
Ottersen, OP ;
de Lanerolle, NC .
LANCET, 2004, 363 (9402) :28-37
[10]   BINDING OF SOLUBLE FORM OF FIBROBLAST SURFACE PROTEIN, FIBRONECTIN, TO COLLAGEN [J].
ENGVALL, E ;
RUOSLAHTI, E .
INTERNATIONAL JOURNAL OF CANCER, 1977, 20 (01) :1-5