Search JIM Advanced Search

Journal of Integrative Medicine ›› 2014, Vol. 12 ›› Issue (6): 476-482.doi: 10.1016/S2095-4964(14)60058-3

• Research Article • Previous Articles     Next Articles

Constructing protein-protein interaction network of hypertension with blood stasis syndrome via digital gene expression sequencing and database mining

Yong-hong Lian, Mei-xia Fang, Li-guo Chen   

  1. Institute of Integrated Chinese and Western Medicine, Medical School of Ji’nan University, Guangzhou 510632, Guangdong Province, China
  • Received:2014-03-03 Accepted:2014-07-17 Online:2014-11-10 Published:2014-11-15

Objective

To construct a protein-protein interaction (PPI) network in hypertension patients with blood-stasis syndrome (BSS) by using digital gene expression (DGE) sequencing and database mining techniques. 

Methods

DGE analysis based on the Solexa Genome Analyzer platform was performed on vascular endothelial cells incubated with serum of hypertension patients with BSS. The differentially expressed genes were filtered by comparing the expression levels between the different experimental groups. Then functional categories and enriched pathways of the unique genes for BSS were analyzed using Database for Annotation, Visualization and Integrated Discovery (DAVID) to select those in the enrichment pathways. Interologous Interaction Database (I2D) was used to construct PPI networks with the selected genes for hypertension patients with BSS. The potential candidate genes related to BSS were identified by comparing the number of relationships among genes. Confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), gene ontology (GO) analysis was used to infer the functional annotations of the potential candidate genes for BSS. 

Results

With gene enrichment analysis using DAVID, a list of 58 genes was chosen from the unique genes. The selected 58 genes were analyzed using I2D, and a PPI network was constructed. Based on the network analysis results, candidate genes for BSS were identified: DDIT3, JUN, HSPA8, NFIL3, HSPA5, HIST2H2BE, H3F3B, CEBPB, SAT1 and GADD45A. Verified through qRT-PCR and analyzed by GO, the functional annotations of the potential candidate genes were explored. 

Conclusion

Compared with previous methodologies reported in the literature, the present DGE analysis and data mining method have shown a great improvement in analyzing BSS.

Key words: Blood-stasis syndrome, Hypertension, Digital gene expression, Protein interaction mapping

"

"

Figure 1

The protein-protein interaction network of the selected 58 genes in the HTBS groups The hubs (the yellow nodes) of the PPI network were: DDIT3, JUN, HSPA8, NFIL3, HSPA5, HIST2H2BE, H3F3B, CEBPB, SAT1 and GADD45A. HTBS: hypertension patients with blood-stasis syndrome."

Figure 2

Results of reverse transcription-polymerase chain reaction are consistent with the previous DGE sequencing results The data are presented as mean ± standard deviation and compared by Student’s t-test (P<0.05)."

[1] Lü AP, Jia HW, Xiao C, Lu QP . Theory of traditional Chinese medicine and therapeutic method of diseases[J]. World J Gastroenterol, 2004,10(13):1854-1856
doi: 10.3748/wjg.v10.i13.1854
[2] Ning SY, Jiang BP, Xu L, Fang TH, Wu MH . Effect of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome[J]. Asian Pac J Trop Med, 2012,5(12):935-938
doi: 10.1016/S1995-7645(12)60177-1
[3] Nicolae M , Mndoiu I. Accurate estimation of gene expression levels from DGE sequencing data. In: Chen J, Wang J, Zelikovsky A. Bioinformatics research and applications; 7th International Symposium, ISBRA 2011, Changsha, China, May 27-29, 2011.
[4] Wang J, Xiong XJ . Evidence-based Chinese medicine for hypertension[J]. Evid Based Complement Alternat Med, 2013,2013:e978398
[5] Xiong X, Yang X, Liu Y, Zhang Y, Wang P, Wang J . Chinese herbal formulas for treating hypertension in traditional Chinese medicine: perspective of modern science[J]. Hypertens Res, 2013,36(7):570-579
doi: 10.1038/hr.2013.18
[6] Wang W . Main points on Chinese hypertension guideline[J]. Yi Xue Yu Zhe Xue Lin Chuang Jue Ce Lun Tan Ban, 2006,27(4):9-13
[7] Chen KJ . Blood stasis syndrome and its treatment with activating blood circulation to remove blood stasis therapy[J]. Chin J Integr Med, 2012,18(12):891-896
doi: 10.1007/s11655-012-1291-5
[8] Chen LG, Hu XQ . On establishment of vascular endothelial cell injury model of blood stasis syndrome based on integration of disease identification and syndrome differentiation[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2007,27(3):267-269
[9] Ewing B, Hillier L, Wendl MC, Green P . Base-calling of automated sequencer traces using phred. I. Accuracy assessment[J]. Genome Res, 1998,8(3):175-185
doi: 10.1101/gr.8.3.175
[10] Trapnell C, Pachter L, Salzberg SL . TopHat: discovering splice junctions with RNA-Seq[J]. Bioinformatics, 2009,25(9):1105-1111
doi: 10.1093/bioinformatics/btp120
[11] Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA . DAVID: database for annotation, visualization, and integrated discovery[J]. Genome Bio, 2003,4(5):P3
doi: 10.1186/gb-2003-4-5-p3
[12] Mills GB, Jurisica I, Yarden Y, Norman JC . Genomic amplicons target vesicle recycling in breast cancer[J]. J Clin Invest, 2009,119(8):2123-2127
[13] Wang J, Yu G . A systems biology approach to characterize biomarkers for blood stasis syndrome of unstable angina patients by integrating microRNA and messenger RNA expression profiling[J]. Evid Based Complement Alternat Med, 2013,2013:510208
[14] Chen SH, Chin CH, Wu HH, Ho CW, Ko MT, Lin CY . Cyto-Hubba: a cytoscape plug-in for hub object analysis in network biology. The 20th International Conference on Genome Informatics, Yokohama, Japan, 2009.
[15] Luo Q, Lian YH, Su JQ, Cheng HH, Hao YK, Zhou FS . Effect of Modified Sijunzi Decoction on 5-HT receptors in intestinal mucosa of IBS-D patients with spleen-deficiency syndrome[J]. Zhongguo Zhong Yi Yao Xin Xi Za Zhi, 2013,20(1):19-21
[16] Benabderrahmane S, Smail-Tabbone M, Poch O, Napoli A, Devignes MD . IntelliGO: a new vector-based semantic similarity measure including annotation origin[J]. BMC Bioinformatics, 2010,11:588
doi: 10.1186/1471-2105-11-588
[17] Li S, Rao XR, Wang SX, Zhang GH, Li XM, Dai XW, Chen KJ . Study on the relationship between blood stasis syndrome and clinical pathology in 227 patients with primary glomerular disease[J]. Chin J Integr Med, 2009,15(3):170-176
doi: 10.1007/s11655-009-0170-4
[18] Zhou YH, Chen LG, Qu Y . Studies on the vascular endothelial cell injury model of blood stasis syndrome from the angle of combination of disease identification and syndrome differentiation[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2011,31(5):696-700
[19] Bahassi el M, Stambrook PJ . Next-generation sequencing technologies: breaking the sound barrier of human genetics[J]. Mutagenesis, 2014,29(5):303-310
doi: 10.1093/mutage/geu031
[20] Lian YH, Li WJ, Chen LG . Potential candidate genes for hypertension with blood stasis syndrome by microarray and databases mining[J]. Int J Biosci Biochem Bioinform, 2014,4(3):150-154
[21] He M, Guo H, Yang X, Zhou L, Zhang X, Cheng L, Zeng H, Hu FB, Tanguay RM, Wu T . Genetic variations in HSPA8 gene associated with coronary heart disease risk in a Chinese population[J]. PLoS One, 2010,5(3):e9684
doi: 10.1371/journal.pone.0009684
[22] Monnier V, Iché-Torres M, Rera M, Contremoulins V, Guichard C, Lalevée N, Tricoire H , Perrin L.dJun and Vri/dNFIL3 are major regulators of cardiac aging in Drosophila[J]. PLoS Genet, 2012,8(11):e1003081
doi: 10.1371/journal.pgen.1003081
[23] Sato Y, Nishio Y, Sekine O, Kodama K, Nagai Y, Nakamura T, Maegawa H, Kashiwagi A . Increased expression of CCAAT/enhancer binding protein-bβ and -δ and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats[J]. Diabetologia, 2007,50(2):481-489
doi: 10.1007/s00125-006-0480-4
[24] Xiong Y, Liebermann D , Hholtzman, EJ, Hoffman B, Eifman-Holtzman O.IL-6 induced Gadd45a-p38 stress response pathway regulates sFlt-1 secretion in HUVEC cells. Society for Maternal-Fetal Medicine: 2009 29th Annual Meeting — The Pregnancy Meeting[J]. Amer J Obstet Gynecol, 2008,199(6 Suppl):S228
[25] Vo TK, de Saint-Hubert M, Morrhaye G, Godard P, Geenen V, Martens HJ, Debacq-Chainiaux F, Swine C, Toussaint O . Transcriptomic biomarkers of the response of hospitalized geriatric patients admitted with heart failure. Comparison to hospitalized geriatric patients with infectious diseases or hip fracture[J]. Mech Ageing Dev, 2011,132(3):131-139
doi: 10.1016/j.mad.2011.02.002
[1] Pranay Soni, Rajesh Choudhary, Surendra H. Bodakhe. Effects of a novel isoflavonoid from the stem bark of Alstonia scholaris against fructose-induced experimental cataract. Journal of Integrative Medicine, 2019, 17(5): 374-382.
[2] Sonia Chew Wen Phang, Uma Devi Palanisamy, Khalid Abdul Kadir. Effects of geraniin (rambutan rind extract) on blood pressure and metabolic parameters in rats fed high-fat diet. Journal of Integrative Medicine, 2019, 17(2): 100-106.
[3] Nathalia Gomes Ribeiro de Moura, Ivan Cordovil, Arthurde Sá Ferreira. Traditional Chinese medicine wrist pulse-taking is associated with pulse waveform analysis and hemodynamics in hypertension. Journal of Integrative Medicine, 2016, 14(2): 100-113.
[4] Nouran A. Aleyeidi, Khaled S. Aseri, Shadia M. Matbouli, Albaraa A. Sulaiamani, Sumayyah A. Kobeisy. Effects of wet-cupping on blood pressure in hypertensive patients: A randomized controlled trial. Journal of Integrative Medicine, 2015, 13(6): 391-399.
[5] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[6] Ya Yuwen, Yu-qi Liu, Yan-ping Wang, Jin-gang Dai, Da-sheng Liu, Yue-xi Wang, Xue-jie Han. The add-on effect of a Chinese herbal formula for patients with resistant hypertension: Study protocol for a pilot cohort study. Journal of Integrative Medicine, 2015, 13(2): 122-128.
[7] Vamsi Reddy, Arvind Sridhar, Roberto F. Machado, Jiwang Chen. High sodium causes hypertension: Evidence from clinical trials and animal experiments. Journal of Integrative Medicine, 2015, 13(1): 1-8.
[8] Yi Chen, De-yu Fu, Yu Chen, Yan-ming He, Xiao-dong Fu, Yan-qiu Xu, Yi Liu, Xiao-tao Feng, Teng Zhang, Wen-jian Wang. Effects of Chinese herbal medicine Yiqi Huaju Formula on hypertensive patients with metabolic syndrome: A randomized, placebo-controlled trial. Journal of Integrative Medicine, 2013, 11(3): 184-194.
[9] Chan Chen, Chang-xun Chen, Xi-min Wu, Rui Wang, Yi-ming Li. Effects of extracts of Radix Scrophulariae on blood pressure in spontaneously hypertensive rats and the underlying mechanisms. Journal of Chinese Integrative Medicine, 2012, 10(9): 1009-1017.
[10] Tao Li-li, Lei Yan. Effects of extracts from Panax ginseng, Panax notoginseng and Ligusticum chuanxiong on expression of β-galactosidase and signal pathway p16-cyclin D/CDK-Rb in vascular smooth muscle cells. Journal of Chinese Integrative Medicine, 2012, 10(1): 76-84.
[11] Rong Fan, Feng He, Yang Wang, Guang-wei Zhong, Yun-hui Li. Changes of protein expression profile in vascular tissues of spontaneously hypertensive rats treated by a compound Chinese herbal medicine. Journal of Chinese Integrative Medicine, 2011, 9(6): 643-650.
[12] Wan-li Gu , Zai-xiang Shi, Yun-xu Yu, Yu-wei Wu, Bao-wei Lu, Ka-kit Hui . Distribution characteristics of syndrome types in essential hypertension. Journal of Chinese Integrative Medicine, 2010, 8(9): 842-847.
[13] Hao Li , Long-tao Liu, Wen-ming Zhao, Jian-gang Liu, Ming-jiang Yao, Yong-xiang Han, Yan-peng Shen, Xing-dong Liu, Li Liu, Xue-mei Wang, Lin-lin Cai, Jie Guan. Traditional Chinese versus integrative treatment in elderly patients with isolated systolic hypertension: A multicenter, randomized, double-blind controlled trial. Journal of Chinese Integrative Medicine, 2010, 8(5): 410-416.
[14] Zhi-qiang Pan, Zhao-qin Fang, Wen-li Lu, Xiao-mei Liu, Dong-yuan Guan, Chao Liang. Differential gene expressions of steroid- and catecholamine-synthesizing enzymes in adrenal gland of rats with different diseases but the same syndromes. Journal of Chinese Integrative Medicine, 2010, 8(4): 352-357.
[15] Yi Chen, Wen-jian Wang. Relationships between insulin resistant and hypertension and traditional Chinese medicine intervention. Journal of Chinese Integrative Medicine, 2010, 8(12): 1114-1118.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[4] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[5] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. Guiding principles of clinical research on mild cognitive impairment (protocol). Journal of Chinese Integrative Medicine, 2008, 6(1): 9-14
[8] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[9] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[10] Xin-jun Wang, Ling-ling Wang . A mechanism of endogenous opioid peptides for rapid onset of acupuncture effect in treatment of depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1014-1017