Weighted gene co-expression network analysis of microarray mRNA expression profiling in response to electroacupuncture

Electroacupuncture (EA) has been extensively considered as a tool for treating diseases and relieving various pains. However, understanding the molecular mechanisms underlying its effect is of high importance. In this study, we performed a weighted gene co-expression network analysis (WGCNA) on data collected from a microarray experiment to investigate the relationship underlying EA within three factors, time, frequency and tissue regions (periaqueductal gray (PAG) and spinal dorsal horn (DH)) as well as the biological implication of gene expression changes. Gene expression on rats in PAG-DH regions induced by EA with 2 Hz and 100 Hz at 1h and 24h were measured using microarray technology. The WGCNA was performed to identify distinct network modules related to EA effects. To find the biological function of genes and pathways, the gene ontology (GO) Consortium was applied and the gene-gene interaction network of top genes in important modules was visualized. We identified one network module (466 genes) which is significantly associated with time, another module (402 genes) significantly related to frequency, and three modules each consisting of 1144, 402 and 3148 genes that are significantly associated with tissue regions. Furthermore, meaningful biological pathways were enriched in association with each of the experimental factors during EA stimulation. Our analysis showed the robustness of WGCNA and revealed important genes within specific modules and pathways which might be activated in response to EA analgesia. The findings may help to clarify the underlying mechanisms of EA and provide references for future verification of this study.

[1]  Jason Jishun Hao,et al.  Review of Clinical Applications of Scalp Acupuncture for Paralysis: An Excerpt From Chinese Scalp Acupuncture , 2012, Global advances in health and medicine.

[2]  Peng-Fei Jiang,et al.  Electroacupuncture Improves Insulin Resistance by Reducing Neuroprotein Y/Agouti-Related Protein Levels and Inhibiting Expression of Protein Tyrosine Phosphatase 1B in Diet-induced Obese Rats. , 2016, Journal of acupuncture and meridian studies.

[3]  P. Nair,et al.  Effect of Electroacupuncture on Function and Quality of Life in Parkinson's Disease: A Case Report , 2013, Acupuncture in medicine : journal of the British Medical Acupuncture Society.

[4]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[5]  L. Hennighausen,et al.  Genome-wide regulation of electro-acupuncture on the neural Stat5-loss-induced obese mice , 2017, PloS one.

[6]  S. Horvath,et al.  Weighted gene coexpression network analysis strategies applied to mouse weight , 2007, Mammalian Genome.

[7]  Qinghua Zhang,et al.  Differences in Neural-Immune Gene Expression Response in Rat Spinal Dorsal Horn Correlates with Variations in Electroacupuncture Analgesia , 2012, PloS one.

[8]  J. Worthington,et al.  Regulation of TGFβ in the immune system: An emerging role for integrins and dendritic cells , 2012, Immunobiology.

[9]  Myeong Soo Lee,et al.  Electroacupuncture reduces neuroinflammatory responses in symptomatic amyotrophic lateral sclerosis model , 2010, Journal of Neuroimmunology.

[10]  Ji-Sheng Han,et al.  Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies , 2003, Trends in Neurosciences.

[11]  A. Firouzjaei,et al.  Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients , 2016, Nutrition & Diabetes.

[12]  Yang Liu,et al.  VisANT 4.0: Integrative network platform to connect genes, drugs, diseases and therapies , 2013, Nucleic Acids Res..

[13]  César A. Hidalgo,et al.  Scale-free networks , 2008, Scholarpedia.

[14]  E. Yang,et al.  Anti-Inflammatory Effects of Electroacupuncture in the Respiratory System of a Symptomatic Amyotrophic Lateral Sclerosis Animal Model , 2011, Neurodegenerative Diseases.

[15]  Andy M. Yip,et al.  Gene network interconnectedness and the generalized topological overlap measure , 2007, BMC Bioinformatics.

[16]  F. Wang,et al.  Effect and Potential Mechanism of Electroacupuncture Add-On Treatment in Patients with Parkinson's Disease , 2015, Evidence-based complementary and alternative medicine : eCAM.

[17]  S. Horvath,et al.  A General Framework for Weighted Gene Co-Expression Network Analysis , 2005, Statistical applications in genetics and molecular biology.

[18]  Jisheng Han,et al.  Genomewide Analysis of Rat Periaqueductal Gray-Dorsal Horn Reveals Time-, Region- and Frequency-Specific mRNA Expression Changes in Response to Electroacupuncture Stimulation , 2014, Scientific Reports.

[19]  R. Albert Scale-free networks in cell biology , 2005, Journal of Cell Science.

[20]  Steve Horvath,et al.  WGCNA: an R package for weighted correlation network analysis , 2008, BMC Bioinformatics.

[21]  P. Sudhakaran Amyotrophic Lateral Sclerosis: An Acupuncture Approach. , 2017, Medical acupuncture.

[22]  Hua Sun,et al.  Electroacupuncture Treatment Improves Neurological Function Associated with Regulation of Tight Junction Proteins in Rats with Cerebral Ischemia Reperfusion Injury , 2014, Evidence-based complementary and alternative medicine : eCAM.

[23]  S. Horvath,et al.  Evidence for anti-Burkitt tumour globulins in Burkitt tumour patients and healthy individuals. , 1967, British Journal of Cancer.

[24]  A. Barabasi,et al.  Hierarchical Organization of Modularity in Metabolic Networks , 2002, Science.