Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Transcriptome Analysis of Traditional Chinese Medicine ‘Kechuanning Plaster’ in the Treatment of Asthma

Author(s): Yanbo Fan, Wei Wang, Zhiwei He, Jingjing Li*, Nian Ding, Lijun Lu, Jun Zhang and Miaomiao Xie

Volume 26, Issue 4, 2023

Published on: 04 August, 2022

Page: [778 - 788] Pages: 11

DOI: 10.2174/1386207325666220524141319

Price: $65

Abstract

Background: Asthma is a severe chronic inflammatory airway disease. Kechuanning plaster has excellent efficacy in the treatment of asthma.

Objective: The aim of this study was to analyze the molecular mechanisms of Kechuanning plaster in the treatment of asthma.

Methods: An asthma model was constructed using Sprague Dawley rats. Differentially expressed genes (DEGs) were screened in three rat groups: the control (normal rats), model (asthma rats), and treatment (asthma rats treated with Kechuanning) groups. After enrichment analysis of the DEGs, the protein-protein interactions (PPIs) of the DEGs were analyzed, and transcription factors and microRNAs (miRNAs) that regulate DEGs were predicted. Finally, western blotting (WB) and immunohistochemical (IHC) analysis was performed to validate protein expression.

Results: A total of 745 DEGs were identified and enriched in 93 Gene Ontology terms and 25 Kyoto Encyclopedia of Genes and Genomes pathways. A PPI network, consisting of 224 protein nodes and 368 edges, was constructed. The nuclear factor of activated T cells 2 (NFATc2) was predicted to have binding sites in 61 DEGs. The miRNA-target interaction network included 24 DEGs and 9 miRNAs. WB and IHC analysis demonstrated that the fatty acid-binding protein 5 (FABP5) and the chemokine (C-X-C motif) ligand 3 (CXCL3) had higher expression in the model group and lower expression in the control and treatment groups.

Conclusion: We concluded that FABP5, CXCL3, suppressor of cytokine signaling 3 (SOCS3), E1A binding protein P300 (EP300), NFATc2, microRNA 495 (miR-495), and miR-30 may play important roles in treating asthma.

Keywords: Asthma, kechuanning plaster, immunohistochemistry, transcriptome analysis traditional Chinese medicine, Immunoglobulin E.

« Previous Next »
Graphical Abstract

[1]
Tay, H.L.; Foster, P.S. Biologics or immunotherapeutics for asthma? Pharmacol. Res., 2020, 158, 104782.
[http://dx.doi.org/10.1016/j.phrs.2020.104782] [PMID: 32275962]
[2]
Russell, R.J.; Brightling, C. Pathogenesis of asthma: Implications for precision medicine. Clin. Sci. (Lond.), 2017, 131(14), 1723-1735.
[http://dx.doi.org/10.1042/CS20160253] [PMID: 28667070]
[3]
Lambrecht, B.N.; Hammad, H.; Fahy, J.V. The cytokines of asthma. Immunity, 2019, 50(4), 975-991.
[http://dx.doi.org/10.1016/j.immuni.2019.03.018] [PMID: 30995510]
[4]
Lieberman, P.L.; Jones, I.; Rajwanshi, R.; Rosén, K.; Umetsu, D.T. Anaphylaxis associated with omalizumab administration: Risk factors and patient characteristics. J. Allergy Clin. Immunol., 2017, 140(6), 1734-1736.e4.
[http://dx.doi.org/10.1016/j.jaci.2017.07.013] [PMID: 28797731]
[5]
Rosenberg, H.F.; Phipps, S.; Foster, P.S. Eosinophil trafficking in allergy and asthma. J. Allergy Clin. Immunol., 2007, 119(6), 1303-1310.
[http://dx.doi.org/10.1016/j.jaci.2007.03.048] [PMID: 17481712]
[6]
Douwes, J.; Gibson, P.; Pekkanen, J.; Pearce, N. Non-eosinophilic asthma: Importance and possible mechanisms. Thorax, 2002, 57(7), 643-648.
[http://dx.doi.org/10.1136/thorax.57.7.643] [PMID: 12096210]
[7]
Shaker, M.; Briggs, A.; Dbouk, A.; Dutille, E.; Oppenheimer, J.; Greenhawt, M. Estimation of health and economic benefits of clinic versus home administration of omalizumab and mepolizumab. J. Allergy Clin. Immunol. Pract., 2020, 8(2), 565-572.
[http://dx.doi.org/10.1016/j.jaip.2019.09.037] [PMID: 31626991]
[8]
Maselli, D.J.; Velez, M.I.; Rogers, L. Reslizumab in the management of poorly controlled asthma: The data so far. J. Asthma Allergy, 2016, 9, 155-162.
[9]
Scheid, V.; Bensky, D.; Ellis, A.; Barolet, R. Chinese herbal medicine: Formulas & strategies; Eastland press, 2009.
[10]
Cheng, Yufeng H.R. Clinical observation on acupoint application of xiazhi kechuanning in the treatment of bronchial asthma with yang deficiency. Heilongjiang J. Trad. Chinese Med., 2014, 43(03), 36-38.
[11]
Tyler, S.R.; Bunyavanich, S. Leveraging -omics for asthma endotyping. J. Allergy Clin. Immunol., 2019, 144(1), 13-23.
[http://dx.doi.org/10.1016/j.jaci.2019.05.015] [PMID: 31277743]
[12]
Bingling, D.S.U. WEN, Contradictory theory. Zhongguo Xiandai Zhongyao, 1982, 6.
[13]
Nikolayeva, O.; Robinson, M.D. edgeR for differential RNA-seq and ChIP-seq analysis: An application to stem cell biology. In: Stem Cell Transcriptional Networks; Springer, 2014; pp. 45-79.
[14]
Robinson, M.D.; McCarthy, D.J.; Smyth, G.K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 2010, 26(1), 139-140.
[http://dx.doi.org/10.1093/bioinformatics/btp616] [PMID: 19910308]
[15]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[16]
Ashburner, M.; Ball, C.A.; Blake, J.A.; Botstein, D.; Butler, H.; Cherry, J.M.; Davis, A.P.; Dolinski, K.; Dwight, S.S.; Eppig, J.T.; Harris, M.A.; Hill, D.P.; Issel-Tarver, L.; Kasarskis, A.; Lewis, S.; Matese, J.C.; Richardson, J.E.; Ringwald, M.; Rubin, G.M.; Sherlock, G. Gene ontology: Tool for the unification of biology. Nat. Genet., 2000, 25(1), 25-29.
[http://dx.doi.org/10.1038/75556] [PMID: 10802651]
[17]
Minoru, K.; Susumu, G. KEGG: Kyoto Encyclopedia of Genes and Genomes; Nucleic Acids Research, 2000, p. 1.
[18]
Szklarczyk, D.; Franceschini, A.; Wyder, S.; Forslund, K.; Heller, D.; Huerta-Cepas, J.; Simonovic, M.; Roth, A.; Santos, A.; Tsafou, K.P.; Kuhn, M.; Bork, P.; Jensen, L.J.; von Mering, C. STRING v10: Protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res., 2015, 43(Database issue), D447-D452.
[http://dx.doi.org/10.1093/nar/gku1003] [PMID: 25352553]
[19]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[20]
Tang, Y.; Li, M.; Wang, J.; Pan, Y.; Wu, F.-X. CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems, 2015, 127, 67-72.
[21]
Aziz, K; Oriol, F; Arnaud, S; Marius, G JASPAR 2018: Update of the open-access database of transcription factor binding profiles and its web framework. Nucleic Acids Res., 2018, 46(D1), D260-D266.
[22]
Grant, C.E.; Bailey, T.L.; Noble, W.S. FIMO: Scanning for occurrences of a given motif; Bioinformatics Oxford, 2011.
[23]
Dweep, H.; Gretz, N. miRWalk2.0: A comprehensive atlas of microRNA-target interactions. Nat. Methods, 2015, 12(8), 697-697.
[http://dx.doi.org/10.1038/nmeth.3485] [PMID: 26226356]
[24]
Holgate, S.T. Pathogenesis of asthma. Clin. Exp. Allergy, 2008, 38(6), 872-897.
[http://dx.doi.org/10.1111/j.1365-2222.2008.02971.x] [PMID: 18498538]
[25]
Veiga, R.V.; Barbosa, H.J.C.; Bernardino, H.S.; Freitas, J.M.; Feitosa, C.A.; Matos, S.M.A.; Alcântara-Neves, N.M.; Barreto, M.L. Multiobjective grammar-based genetic programming applied to the study of asthma and allergy epidemiology. BMC Bioinformatics, 2018, 19(1), 245.
[http://dx.doi.org/10.1186/s12859-018-2233-z] [PMID: 29940834]
[26]
Ye Lu, T.B.; Guo, Y.; Wu, K. Du leyi. Observation on the therapeutic effect of Kangmin Zhike decoction combined with Kechuanning acupoint application on children with cough variant asthma of wind cold type. Shanghai J. Traditional Chinese Med., 2019, 53(12), 56-60.
[27]
O’Shea, J.J.; Murray, P.J. Cytokine signaling modules in inflammatory responses. Immunity, 2008, 28(4), 477-487.
[http://dx.doi.org/10.1016/j.immuni.2008.03.002] [PMID: 18400190]
[28]
Seki, Y.; Inoue, H.; Nagata, N.; Hayashi, K.; Fukuyama, S.; Matsumoto, K.; Komine, O.; Hamano, S.; Himeno, K.; Inagaki-Ohara, K.; Cacalano, N.; O’Garra, A.; Oshida, T.; Saito, H.; Johnston, J.A.; Yoshimura, A.; Kubo, M. SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses. Nat. Med., 2003, 9(8), 1047-1054.
[http://dx.doi.org/10.1038/nm896] [PMID: 12847520]
[29]
Paul, B.; Mishra, V.; Chaudhury, B.; Awasthi, A.; Das, A.B.; Saxena, U.; Saxena, A.; Chauhan, L.K.; Kumar, P.; Raisuddin, S. Status of Stat3 in an ovalbumin-induced mouse model of asthma: Analysis of the role of Socs3 and IL-6. Int. Arch. Allergy Immunol., 2009, 148(2), 99-108.
[http://dx.doi.org/10.1159/000155740] [PMID: 18799889]
[30]
Gayther, S.A.; Batley, S.J.; Linger, L.; Bannister, A.; Thorpe, K.; Chin, S.F.; Daigo, Y.; Russell, P.; Wilson, A.; Sowter, H.M.; Delhanty, J.D.; Ponder, B.A.; Kouzarides, T.; Caldas, C. Mutations truncating the EP300 acetylase in human cancers. Nat. Genet., 2000, 24(3), 300-303.
[http://dx.doi.org/10.1038/73536] [PMID: 10700188]
[31]
Lee, S.Y.; Won, H.K.; Kim, B.K.; Kim, S.H.; Chang, Y.S.; Cho, S.H.; Kelly, H.W.; Tantisira, K.G.; Park, H.W. Identification of a key gene module associated with glucocorticoid- induced derangement in bone mineral density in patients with asthma. Sci. Rep., 2019, 9(1), 20133.
[http://dx.doi.org/10.1038/s41598-019-56656-9] [PMID: 31882850]
[32]
Suojalehto, H.; Kinaret, P.; Kilpeläinen, M.; Toskala, E.; Ahonen, N.; Wolff, H.; Alenius, H.; Puustinen, A. Level of fatty acid binding protein 5 (FABP5) is increased in sputum of allergic asthmatics and links to airway remodeling and inflammation. PLoS One, 2015, 10(5), e0127003-e0127003.
[http://dx.doi.org/10.1371/journal.pone.0127003] [PMID: 26020772]
[33]
Salter, B.; Pray, C.; Radford, K.; Martin, J.G.; Nair, P. Regulation of human airway smooth muscle cell migration and relevance to asthma. Respir. Res., 2017, 18(1), 156.
[http://dx.doi.org/10.1186/s12931-017-0640-8] [PMID: 28814293]
[34]
Karwot, R.; übel, C.; Bopp, T.; Schmitt, E.; Finotto, S. Increased immunosuppressive function of CD4+CD25+Foxp3+GITR+ T regulatory cells from NFATc2(-/-) mice controls allergen-induced experimental asthma. Immunobiology, 2012, 217(9), 905-911.
[35]
Karwot, R.; Maxeiner, J.H.; Schmitt, S.; Scholtes, P.; Hausding, M.; Lehr, H.A.; Glimcher, L.H.; Finotto, S. Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T Cells1. J. Immunol., 2008, 181(9), 6148-6157.
[36]
Karwot, R.; Maxeiner, J.; Schmitt, S.; Scholtes, P.; Sauer, K.; Hausding, M.; Doganci, A.; Lehr, H.; Galle, P.; Finotto, S. Essential role of NFATc2 in CD8+ T cells in experimental model of asthma. Pneumologie, 2007, 61(01), A4.
[http://dx.doi.org/10.1055/s-2007-967225]
[37]
Tan, A.H-M.; Wong, S-C.; Lam, K-P. Regulation of mouse inducible costimulator (ICOS) expression by Fyn-NFATc2 and ERK signaling in T cells. J. Biol. Chem., 2006, 281(39), 28666-28678.
[http://dx.doi.org/10.1074/jbc.M604081200] [PMID: 16880206]
[38]
Coyle, A.J.; Gutierrez-Ramos, J.C. The role of ICOS and other costimulatory molecules in allergy and asthma. Springer Semin. Immunopathol., 2004, 25(3-4), 349-359.
[http://dx.doi.org/10.1007/s00281-003-0154-y] [PMID: 14999428]
[39]
Moens, L.; Gouwy, M.; Bosch, B.; Pastukhov, O.; Nieto-Patlàn, A.; Siler, U.; Bucciol, G.; Mekahli, D.; Vermeulen, F.; Desmet, L.; Maebe, S.; Flipts, H.; Corveleyn, A.; Moshous, D.; Philippet, P.; Tangye, S.G.; Boisson, B.; Casanova, J-L.; Florkin, B.; Struyf, S.; Reichenbach, J.; Bustamante, J.; Notarangelo, L.D.; Meyts, I. Human DOCK2 deficiency: Report of a novel mutation and evidence for neutrophil dysfunction. J. Clin. Immunol., 2019, 39(3), 298-308.
[http://dx.doi.org/10.1007/s10875-019-00603-w] [PMID: 30838481]
[40]
LeMessurier, K.S.; Palipane, M.; Tiwary, M.; Gavin, B.; Samarasinghe, A.E. Chronic features of allergic asthma are enhanced in the absence of resistin-like molecule-beta. Sci. Rep., 2018, 8(1), 7061-7061.
[http://dx.doi.org/10.1038/s41598-018-25321-y] [PMID: 29728628]
[41]
Melén, E.; Himes, B.E.; Brehm, J.M.; Boutaoui, N.; Klanderman, B.J.; Sylvia, J.S.; Lasky-Su, J. Analyses of shared genetic factors between asthma and obesity in children. J. Allergy Clin. Immunol., 2010, 126(3), 631-637.
[42]
Pasaje, C.; Kim, J.-H.; Park, B.; Park, J.-S.; Uh, S.-T.; Kim, M.-K.; Park, C.-S.; Shin, H. UBE3C genetic variations as potent markers of nasal polyps in Korean asthma patients. J. Human Genet., 2011, 56, 797-800.
[43]
Eulalio, A.; Rehwinkel, J.; Stricker, M.; Huntzinger, E.; Yang, S-F.; Doerks, T.; Dorner, S.; Bork, P.; Boutros, M.; Izaurralde, E. Target-specific requirements for enhancers of decapping in miRNA-mediated gene silencing. Genes Dev., 2007, 21(20), 2558-2570.
[http://dx.doi.org/10.1101/gad.443107] [PMID: 17901217]
[44]
Loginov, V.I.; Filippova, E.A.; Kurevlev, S.V.; Fridman, M.V.; Burdennyy, A.M.; Braga, E.A. Suppressive and hypermethylated microRNAs in the pathogenesis of breast cancer. Russ. J. Genet., 2018, 54(7), 770-787.
[http://dx.doi.org/10.1134/S1022795418070086]
[45]
Boominathan, L. The guardians of the genome dependent tumor suppressor miRNAs network., 2009.
[46]
Li, Z.; Hassan, M.Q.; Volinia, S.; van Wijnen, A.J.; Stein, J.L.; Croce, C.M.; Lian, J.B.; Stein, G.S. A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc. Natl. Acad. Sci. USA, 2008, 105(37), 13906-13911.
[http://dx.doi.org/10.1073/pnas.0804438105] [PMID: 18784367]
[47]
Wu, T.; Zhou, H.; Hong, Y.; Li, J.; Jiang, X.; Huang, H. miR-30 family members negatively regulate osteoblast differentiation. J. Biol. Chem., 2012, 287(10), 7503-7511.
[http://dx.doi.org/10.1074/jbc.M111.292722] [PMID: 22253433]
[48]
Cheng, C.W.; Wang, H.W.; Chang, C.W.; Chu, H.W.; Chen, C.Y.; Yu, J.C.; Chao, J.I.; Liu, H.F.; Ding, S.L.; Shen, C.Y. MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer. Breast Cancer Res. Treat., 2012, 134(3), 1081-1093.
[http://dx.doi.org/10.1007/s10549-012-2034-4] [PMID: 22476851]
[49]
Yang, S.J.; Yang, S.Y.; Wang, D.D.; Chen, X.; Shen, H.Y.; Zhang, X.H.; Zhong, S.L.; Tang, J.H.; Zhao, J.H. The miR-30 family: Versatile players in breast cancer. Tumour Biol., 2017, 39(3), 1010428317692204.
[http://dx.doi.org/10.1177/1010428317692204] [PMID: 28347244]
[50]
Scagnolari, C.; Zingariello, P.; Vecchiet, J.; Selvaggi, C.; Racciatti, D.; Taliani, G.; Riva, E.; Pizzigallo, E.; Antonelli, G. Differential expression of interferon-induced microRNAs in patients with chronic hepatitis C virus infection treated with pegylated interferon alpha. Virol. J., 2010, 7(1), 311.
[http://dx.doi.org/10.1186/1743-422X-7-311] [PMID: 21070682]
[51]
Wu, G.; Yang, G.; Zhang, R.; Xu, G.; Zhang, L.; Wen, W.; Lu, J.; Liu, J.; Yu, Y. Altered microRNA expression profiles of extracellular vesicles in nasal mucus from patients with allergic rhinitis. Allergy Asthma Immunol. Res., 2015, 7(5), 449-457.
[http://dx.doi.org/10.4168/aair.2015.7.5.449] [PMID: 26122505]
[52]
Testa, D.; Bari, M.D.; Nunziata, M.; Cristofaro, G.D.; Motta, G. Allergic rhinitis and asthma assessment of risk factors in pediatric patients: A systematic review. Inter. J. Pediatr. Otorhinolaryngol., 2019, 129(109759)

Rights & Permissions Print Cite
Article Metrics
30
3
© 2024 Bentham Science Publishers | Privacy Policy