Introducing GATA3 as a prominent player in Crohn’s Disease GATA3 and Crohn’s Disease
Gastroenterology and Hepatology from Bed to Bench,
9 December 2020
Aim: This study was aimed at gene assessment of crohn's disease (CD) through protein-protein interaction (PPI) network analysis to find crucial genes.
Background: CD is one of the main subtypes of inflammatory bowel diseases (IBD), which affects any part of the gastrointestinal tract. PPI network analysis is a suitable tool to clarify a critical gene as a drug target or diagnostic biomarker for these types of diseases.
Methods: Gene expression profile GSE126124 of 20 CD patients and 20 healthy controls was obtained from the Gene Expression Omnibus (GEO) database. RNA profile of peripheral blood mononuclear cells (PBMCs) and colon biopsy samples of the studied groups was investigated. The significant genes were selected and analyzed via the PPI network by Cytoscape software. Gene ontology enrichment for the hubs, bottlenecks, and hub-bottlenecks was done via the CluGO plugin of Cytoscape software.
Results: eighty-one differentially expressed genes (DEGs) among 250 initial DEGs were highlighted as significant by FC>2 and p-value ≤ 0.05, and 69 significant DEGs were used for PPI network construction. The network was characterized by poor connections, so 20 first neighbors were added to form a scale-free network. The main connected component was included 39 query DEGs and 20 added first neighbors. Three clusters of biological processes related to the crucial genes were identified and discussed.
Conclusion: The result of this study indicated that GATA3 has a key role in CD pathogenesis and could be a possible drug target or diagnostic biomarker for crohn’s disease.
Keywords: Crohn’s Disease, Genes, Gene Ontology, GATA3 Transcription Factor
- Crohn’s Disease, Genes, Gene Ontology, GATA3 Transcription Factor
2. Lemmens B, De Hertogh G, Sagaert X. Inflammatory Bowel Diseases. In: McManus LM, Mitchell RN, editors. Pathobiology of Human Disease. San Diego. Academic Press, 2014;p:1297-304.
3. Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev 2002;15(1):79-94.
4. Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, et al. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study. The Lancet 2016;387(10014):156-67.
5. Moura FA, Goulart MOF. Inflammatory Bowel Diseases: The Crosslink Between Risk Factors and Antioxidant Therapy. In: Gracia-Sancho J, Salvadó J, editors. Gastrointestinal Tissue. Academic Press, 2017;p:99-112.
6. Baumgart DC, Sandborn WJ. Crohn's disease. The Lancet 2012;380(9853):1590-605.
7. Pimentel AM, Rocha R, Santana GO. Crohn's disease of esophagus, stomach and duodenum. World J Gastrointest Pharmacol Ther 2019;10(2):35-49.
8. Rostami-Nejad M, Yazdi MH, Nikfar S, Rezaie A, Abdollahi M. Potential Vaccines for Treating Crohn's Disease. Iran Biomed J 2020;24(1):1-14.
9. Michail S, Bultron G, Depaolo RW. Genetic variants associated with Crohn's disease. Appl Clin Genet 2013;6:25-32.
10. Loddo I, Romano C. Inflammatory Bowel Disease: Genetics, Epigenetics, and Pathogenesis. Front Immunol 2015;6(551).
11. Bianco AM, Girardelli M, Tommasini A. Genetics of inflammatory bowel disease from multifactorial to monogenic forms. World J Gastroenterol 2015;21(43):12296-310.
12. Oshima S, Watanabe M. Genetic and environmental factors drive personalized medicine for Crohn's disease. J Clin Investig 2018;128(11):4758-60.
13. Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Clin Pract Gastr 2006;3(7):390-407.
14. Safari-Alighiarloo N, Taghizadeh M, Rezaei-Tavirani M, Goliaei B, Peyvandi AA. Protein-protein interaction networks (PPI) and complex diseases. Gastroenterol Hepatol Bed Bench 2014;7(1):17.
15. Rezaei Tavirani M, Mansouri V, Rezaei Tavirani S, Hesami Tackallou S, Rostami-Nejad M. Gliosarcoma protein-protein interaction network analysis and gene ontology. Int J Cancer Manag 2018;11(5).
16. Asadzadeh-Aghdaee H, Shahrokh S, Norouzinia M, Hosseini M, Keramatinia A, Jamalan M, et al. Introduction of inflammatory bowel disease biomarkers panel using protein-protein interaction (PPI) network analysis. Gastroenterol Hepatol Bed Bench 2016;9(Suppl1):S8-S13.
17. Brandes U. A faster algorithm for betweenness centrality. J Math Sociol 2001;25(2):163-77.
18. Amiri-Dashatan N, Koushki M, Abbaszadeh H-A, Rostami-Nejad M, Rezaei-Tavirani M. Proteomics Applications in Health: Biomarker and Drug Discovery and Food Industry. Iran J Pharm Res 2018;17(4):1523-36.
19. Vella D, Marini S, Vitali F, Di Silvestre D, Mauri G, Bellazzi R. MTGO: PPI Network Analysis Via Topological and Functional Module Identification. Sci Rep 2018;8(1):5499.
20. Rao VS, Srinivas K, Sujini GN, Kumar GNS. Protein-protein interaction detection: methods and analysis. Int J Proteomics 2014;2014:147648-.
21. Xu X-R, Liu C-Q, Feng B-S, Liu Z-J. Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease. World J Gastroenterol 2014;20(12):3255-64.
22. Watanabe M, Yamazaki M, Kanai T. Mucosal T cells as a target for treatment of IBD. J Gastroenterol 2003;38.
23. Andreu-Ballester JC, Pérez-Griera J, Garcia-Ballesteros C, Amigo V, Catalán-Serra I, Monforte-Albalat A, et al. Deficit of Interleukin-7 in Serum of Patients with Crohn's Disease. Inflamm Bowel Dis 2012;19(2):E30-E1.
24. Kader HA, Tchernev VT, Satyaraj E, Lejnine S, Kotler G, Kingsmore SF, et al. Protein microarray analysis of disease activity in pediatric inflammatory bowel disease demonstrates elevated serum PLGF, IL-7, TGF-beta1, and IL-12p40 levels in Crohn's disease and ulcerative colitis patients in remission versus active disease. Am J Gastroenterol 2005;100(2):414-23.
25. Wang Y, Su MA, Wan YY. An essential role of the transcription factor GATA-3 for the function of regulatory T cells. Immunity 2011;35(3):337-48.
26. Li J, Ueno A, Iacucci M, Fort Gasia M, Jijon HB, Panaccione R, et al. Crossover Subsets of CD4+ T Lymphocytes in the Intestinal Lamina Propria of Patients with Crohn’s Disease and Ulcerative Colitis. Dig Dis Sci 2017;62(9):2357-68.
27. Lee S, Kim SM, Lee RT. Thioredoxin and thioredoxin target proteins: from molecular mechanisms to functional significance. Antioxid Redox Signal 2013;18(10):1165-207.
28. Rand JD, Grant CM. The thioredoxin system protects ribosomes against stress-induced aggregation. Mol Biol Cell 2006;17(1):387-401.
29. Masutani H, Ueda S, Yodoi J. The thioredoxin system in retroviral infection and apoptosis. Cell Death Differ 2005;12(1):991-8.
30. Bertini R, Howard OM, Dong HF, Oppenheim JJ, Bizzarri C, Sergi R, et al. Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells. J Exp Med 1999;189(11):1783-9.
31. Powis G, Mustacich D, Coon A. The role of the redox protein thioredoxin in cell growth and cancer. Free Radic Biol Med 2000;29(3):312-22.
32. Soufli I, Toumi R, Rafa H, Chafia T. Cytokines and Nitric Oxide in Immunopathogenesis of IBD and Potential Therapeutic Approaches. in: New Insights into Inflammatory Bowel Disease. InTech, 2016.
33. Biasi F, Leonarduzzi G, Oteiza PI, Poli G. Inflammatory bowel disease: mechanisms, redox considerations, and therapeutic targets. Antioxid Redox Signal 2013;19(14):1711-47.
34. Tian T, Wang Z, Zhang J. Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies. Oxid Med Cell Longev 2017;2017:4535194.
35. Tamaki H, Nakamura H, Nishio A, Nakase H, Ueno S, Uza N, et al. Human thioredoxin-1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production. Gastroenterology 2006;131(4):1110-21.
36. Ge Y, Sun M, Wu W, Ma C, Zhang C, He C, et al. MicroRNA-125a suppresses intestinal mucosal inflammation through targeting ETS-1 in patients with inflammatory bowel diseases. J Autoimmun 2019;101:109-20.
37. Li L, Miao X, Ni R, Miao X, Wang L, Gu X, et al. Epithelial-specific ETS-1 (ESE1/ELF3) regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation. Immunol Res 2015;62(2):198-212.
38. Genua M, Sgambato A, Danese S. Editorial: CCR7 is required for leukocyte egression in an experimental model of Crohn's disease-like ileitis. J Leukoc Biol 2015;97(6):1000-2.
39. Danese S, Gasbarrini A. Chemokines in inflammatory bowel disease. J Clin Pathol 2005;58(10):1025-7.
40. Worbs T, Förster R. A key role for CCR7 in establishing central and peripheral tolerance. Trends Immunol 2007;28(6):274-80.
41. Kawashima D, Oshitani N, Jinno Y, Watanabe K, Nakamura S, Higuchi K, et al. Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease. J Clin Pathol 2005;58(10):1057-63.
42. Ledbetter JA, Linsley PS. CD28. In: Delves PJ, editor. Encyclopedia of Immunology (Second Edition). Oxford: Elsevier, 1998;p:482-3.
43. van Nieuwenhuijze A, Liston A. Chapter Four - The Molecular Control of Regulatory T Cell Induction. In: Liston A, editor. Progress in Molecular Biology and Translational Science. 136 Academic Press, 2015;p: 69-97.
44. De Tena JG, Manzano L, Leal JC, San Antonio E, Sualdea V, Álvarez-Mon M. Active Crohn's disease patients show a distinctive expansion of circulating memory CD4+ CD45RO+ CD28 null T cells. J clin immunol 2004;24(2):185-96.
45. Soldevila G, Raman C, Lozano F. The immunomodulatory properties of the CD5 lymphocyte receptor in health and disease. Curr Opin Immunol 2011;23(3):310-8.
46. Voisinne G, Gonzalez de Peredo A, Roncagalli R. CD5, an Undercover Regulator of TCR Signaling. Front Immunol 2018;9(2900).
47. Dalloul A. CD5: a safeguard against autoimmunity and a shield for cancer cells. Autoimmun Rev 2009;8(4):349-53.
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