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Shahriary, Alireza, Sisakht, Mohsen, Arabfard, Masoud, Behmard, Esmaeil, Najafi, Ali. (1403). Targeting Trefoil Factor Family 3 in Obstructive Airway Diseases: A Computational Approach to Novel Therapeutics. سامانه مدیریت نشریات علمی, (), -. doi: 10.30476/ijms.2024.101737.3435
Alireza Shahriary; Mohsen Sisakht; Masoud Arabfard; Esmaeil Behmard; Ali Najafi. "Targeting Trefoil Factor Family 3 in Obstructive Airway Diseases: A Computational Approach to Novel Therapeutics". سامانه مدیریت نشریات علمی, , , 1403, -. doi: 10.30476/ijms.2024.101737.3435
Shahriary, Alireza, Sisakht, Mohsen, Arabfard, Masoud, Behmard, Esmaeil, Najafi, Ali. (1403). 'Targeting Trefoil Factor Family 3 in Obstructive Airway Diseases: A Computational Approach to Novel Therapeutics', سامانه مدیریت نشریات علمی, (), pp. -. doi: 10.30476/ijms.2024.101737.3435
Shahriary, Alireza, Sisakht, Mohsen, Arabfard, Masoud, Behmard, Esmaeil, Najafi, Ali. Targeting Trefoil Factor Family 3 in Obstructive Airway Diseases: A Computational Approach to Novel Therapeutics. سامانه مدیریت نشریات علمی, 1403; (): -. doi: 10.30476/ijms.2024.101737.3435

Targeting Trefoil Factor Family 3 in Obstructive Airway Diseases: A Computational Approach to Novel Therapeutics

Iranian Journal of Medical Sciences
مقالات آماده انتشار، اصلاح شده برای چاپ، انتشار آنلاین از تاریخ 28 مهر 1403    اصل مقاله (2.5 M)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/ijms.2024.101737.3435
نویسندگان
Alireza Shahriary1؛ Mohsen Sisakht2؛ Masoud Arabfard1؛ Esmaeil Behmard3؛ Ali Najafi* 4
1Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
3School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
4Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
چکیده
Background: Airway remodeling, a hallmark of chronic obstructive pulmonary disease (COPD) and mustard lung disease, is influenced by the Trefoil Factor 3 (TFF3). This study sought to pinpoint a compound with minimal toxicity that can effectively suppress TFF3 expression and activity.
Methods: We employed an integrative approach, combining gene expression analysis, molecular docking, and molecular dynamics simulations to identify potential TFF3 inhibitors. Gene expression analysis utilized Z-scores from the Library of Integrated Network-Based Cellular Signatures (LINCS) database to identify compounds altering TFF3 expression. Drug-like properties were assessed through Lipinski’s “Rule of Five.” Molecular docking was conducted with AutoDock Vina (version 1.1.2), and molecular dynamics simulations were performed using Groningen Machine for Chemical Simulations (GROMACS) version 5.1. Toxicity evaluation leveraged a Graph Convolutional Network (GCN). Statistical significance was set at P<0.05.
Results: Eight of the compounds assessed significantly reduced TFF3 expression, with binding affinities (ΔG) ranging from -7 to -9.4 kcal/mol. Notably, genistein emerged as the frontrunner, showcasing potent TFF3 downregulation, minimal toxicity, and a robust inhibitory profile, as evidenced by molecular dynamics simulations. The significance of gene expression changes was indicated by Z-scores provided by the LINCS database rather than exact P values.
Conclusion: Genistein holds promise as a therapeutic agent for TFF3-mediated conditions, including mustard lung disease. Its potential to address the current therapeutic gaps is evident, but its clinical utility necessitates further in vitro and in vivo validation.
کلیدواژه‌ها
Trefoil factor 3, airway remodeling؛ Lung diseases, obstructive؛ Genistein
مراجع
  1. Liu P, Wang Y, Chen C, Liu H, Ye J, Zhang X, et al. Research trends on airway remodeling: A bibliometrics analysis. Heliyon. 2024;10:e24824. doi: 10.1016/j.heliyon.2024.e24824. PubMed PMID: 38333835; PubMed Central PMCID: PMCPMC10850909.
  2. Shahriary A, Seyedzadeh MH, Ahmadi A, Salimian J. The footprint of TGF-beta in airway remodeling of the mustard lung. Inhal Toxicol. 2015;27:745-53. doi: 10.3109/08958378.2015.1116645. PubMed PMID: 26606948.
  3. Fang L, Sun Q, Roth M. Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma. Int J Mol Sci. 2020;21. doi: 10.3390/ijms21030757. PubMed PMID: 31979396; PubMed Central PMCID: PMCPMC7037330.
  4. Wang Y, Xu J, Meng Y, Adcock IM, Yao X. Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:3341-8. doi: 10.2147/COPD.S176122. PubMed PMID: 30349237; PubMed Central PMCID: PMCPMC6190811.
  5. Marzouni ET, Dorcheh SP, Nejad-Moghaddam A, Ghanei M, Goodarzi H, Hosseini SE, et al. Adipose-derived mesenchymal stem cells ameliorate lung epithelial injury through mitigating of oxidative stress in mustard lung. Regen Med. 2020. doi: 10.2217/rme-2020-0051. PubMed PMID: 32935623.
  6. Najafi A, Masoudi-Nejad A, Ghanei M, Nourani MR, Moeini A. Pathway reconstruction of airway remodeling in chronic lung diseases: a systems biology approach. PLoS One. 2014;9:e100094. doi: 10.1371/journal.pone.0100094. PubMed PMID: 24978043; PubMed Central PMCID: PMCPMC4076832.
  7. Weste J, Houben T, Harder S, Schluter H, Lucke E, Schreiber J, et al. Different Molecular Forms of TFF3 in the Human Respiratory Tract: Heterodimerization with IgG Fc Binding Protein (FCGBP) and Proteolytic Cleavage in Bronchial Secretions. Int J Mol Sci. 2022;23. doi: 10.3390/ijms232315359. PubMed PMID: 36499686; PubMed Central PMCID: PMCPMC9737082.
  8. Viby NE, Pedersen L, Lund TK, Kissow H, Backer V, Nexo E, et al. Trefoil factor peptides in serum and sputum from subjects with asthma and COPD. Clin Respir J. 2015;9:322-9. doi: 10.1111/crj.12146. PubMed PMID: 24720774.
  9. Mihalj M, Bujak M, Butkovic J, Zubcic Z, Tolusic Levak M, Ces J, et al. Differential Expression of TFF1 and TFF3 in Patients Suffering from Chronic Rhinosinusitis with Nasal Polyposis. Int J Mol Sci. 2019;20. doi: 10.3390/ijms20215461. PubMed PMID: 31683988; PubMed Central PMCID: PMCPMC6862153.
  10. Doubkova M, Karpisek M, Mazoch J, Skrickova J, Doubek M. Prognostic significance of surfactant protein A, surfactant protein D, Clara cell protein 16, S100 protein, trefoil factor 3, and prostatic secretory protein 94 in idiopathic pulmonary fibrosis, sarcoidosis, and chronic pulmonary obstructive disease. Sarcoidosis Vasc Diffuse Lung Dis. 2016;33:224-34. PubMed PMID: 27758987.
  11. Yang Y, Lin Z, Lin Q, Bei W, Guo J. Pathological and therapeutic roles of bioactive peptide trefoil factor 3 in diverse diseases: recent progress and perspective. Cell Death Dis. 2022;13:62. doi: 10.1038/s41419-022-04504-6. PubMed PMID: 35039476; PubMed Central PMCID: PMCPMC8763889.
  12. Zhu Y, Zhao S, Deng Y, Gordillo R, Ghaben AL, Shao M, et al. Hepatic GALE Regulates Whole-Body Glucose Homeostasis by Modulating Tff3 Expression. Diabetes. 2017;66:2789-99. doi: 10.2337/db17-0323. PubMed PMID: 28877911; PubMed Central PMCID: PMCPMC5652600.
  13. Jarva MA, Lingford JP, John A, Soler NM, Scott NE, Goddard-Borger ED. Trefoil factors share a lectin activity that defines their role in mucus. Nat Commun. 2020;11:2265. doi: 10.1038/s41467-020-16223-7. PubMed PMID: 32404934; PubMed Central PMCID: PMCPMC7221086.
  14. Braga Emidio N, Brierley SM, Schroeder CI, Muttenthaler M. Structure, Function, and Therapeutic Potential of the Trefoil Factor Family in the Gastrointestinal Tract. ACS Pharmacol Transl Sci. 2020;3:583-97. doi: 10.1021/acsptsci.0c00023. PubMed PMID: 32832864; PubMed Central PMCID: PMCPMC7432662.
  15. Hoffmann W. Trefoil factor family (TFF) peptides. Encyclopedia. 2021;1:974-87. doi: 10.3390/encyclopedia1030074.
  16. Keenan AB, Jenkins SL, Jagodnik KM, Koplev S, He E, Torre D, et al. The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations. Cell Syst. 2018;6:13-24. doi: 10.1016/j.cels.2017.11.001. PubMed PMID: 29199020; PubMed Central PMCID: PMCPMC5799026.
  17. Pilarczyk M, Fazel-Najafabadi M, Kouril M, Shamsaei B, Vasiliauskas J, Niu W, et al. Connecting omics signatures and revealing biological mechanisms with iLINCS. Nat Commun. 2022;13:4678. doi: 10.1038/s41467-022-32205-3. PubMed PMID: 35945222; PubMed Central PMCID: PMCPMC9362980.
  18. Colan SD. The why and how of Z scores. J Am Soc Echocardiogr. 2013;26:38-40. doi: 10.1016/j.echo.2012.11.005. PubMed PMID: 23261367.
  19. Bastholm SK, Samson MH, Becher N, Hansen LK, Stubbe PR, Chronakis IS, et al. Trefoil factor peptide 3 is positively correlated with the viscoelastic properties of the cervical mucus plug. Acta Obstet Gynecol Scand. 2017;96:47-52. doi: 10.1111/aogs.13038. PubMed PMID: 27731893.
  20. Sohel M, Biswas P, Al Amin M, Hossain MA, Sultana H, Dey D, et al. Genistein, a potential phytochemical against breast cancer treatment-insight into the molecular mechanisms. Processes. 2022;10:415.
  21. Yu X, Yan J, Li Y, Cheng J, Zheng L, Fu T, et al. Inhibition of castration-resistant prostate cancer growth by genistein through suppression of AKR1C3. Food Nutr Res. 2023;67. doi: 10.29219/fnr.v67.9024. PubMed PMID: 36794010; PubMed Central PMCID: PMCPMC9899042.
  22. Alorda-Clara M, Torrens-Mas M, Morla-Barcelo PM, Roca P, Sastre-Serra J, Pons DG, et al. High Concentrations of Genistein Decrease Cell Viability Depending on Oxidative Stress and Inflammation in Colon Cancer Cell Lines. Int J Mol Sci. 2022;23. doi: 10.3390/ijms23147526. PubMed PMID: 35886874; PubMed Central PMCID: PMCPMC9323408.
  23. Zhao L, Wang Y, Liu J, Wang K, Guo X, Ji B, et al. Protective Effects of Genistein and Puerarin against Chronic Alcohol-Induced Liver Injury in Mice via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms. J Agric Food Chem. 2016;64:7291-7. doi: 10.1021/acs.jafc.6b02907. PubMed PMID: 27609057.
  24. Kushwaha AC, Mohanbhai SJ, Sardoiwala MN, Jaganathan M, Karmakar S, Roy Choudhury S. Nanoemulsified Genistein and Vitamin D Mediated Epigenetic Regulation to Inhibit Osteoporosis. ACS Biomater Sci Eng. 2022;8:3810-8. doi: 10.1021/acsbiomaterials.2c00165. PubMed PMID: 36005299.
  25. Li R, Robinson M, Ding X, Geetha T, Al-Nakkash L, Broderick TL, et al. Genistein: A focus on several neurodegenerative diseases. J Food Biochem. 2022;46:e14155. doi: 10.1111/jfbc.14155. PubMed PMID: 35460092.
  26. Li R, Ding X, Geetha T, Fadamiro M, St Aubin CR, Shim M, et al. Effects of Genistein and Exercise Training on Brain Damage Induced by a High-Fat High-Sucrose Diet in Female C57BL/6 Mice. Oxid Med Cell Longev. 2022;2022:1560435. doi: 10.1155/2022/1560435. PubMed PMID: 35620577; PubMed Central PMCID: PMCPMC9129997.
  27. Rasheed S, Rehman K, Shahid M, Suhail S, Akash MSH. Therapeutic potentials of genistein: New insights and perspectives. J Food Biochem. 2022;46:e14228. doi: 10.1111/jfbc.14228. PubMed PMID: 35579327.
  28. Gan M, Chen X, Chen Z, Chen L, Zhang S, Zhao Y, et al. Genistein Alleviates High-Fat Diet-Induced Obesity by Inhibiting the Process of Gluconeogenesis in Mice. Nutrients. 2022;14. doi: 10.3390/nu14081551. PubMed PMID: 35458112; PubMed Central PMCID: PMCPMC9032493.
  29. Nasimi Doost Azgomi R, Moini Jazani A, Karimi A, Pourreza S. Potential roles of genistein in polycystic ovary syndrome: A comprehensive systematic review. Eur J Pharmacol. 2022;933:175275. doi: 10.1016/j.ejphar.2022.175275. PubMed PMID: 36108737.
  30. Ding Q, Pi A, Hao L, Xu T, Zhu Q, Shu L, et al. Genistein Protects against Acetaldehyde-Induced Oxidative Stress and Hepatocyte Injury in Chronic Alcohol-Fed Mice. J Agric Food Chem. 2023;71:1930-43. doi: 10.1021/acs.jafc.2c05747. PubMed PMID: 36653166.
  31. Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM. Genistein: A Review on its Anti-Inflammatory Properties. Front Pharmacol. 2022;13:820969. doi: 10.3389/fphar.2022.820969. PubMed PMID: 35140617; PubMed Central PMCID: PMCPMC8818956.
  32. Li Y, Zhang JJ, Chen RJ, Chen L, Chen S, Yang XF, et al. Genistein mitigates oxidative stress and inflammation by regulating Nrf2/HO-1 and NF-kappaB signaling pathways in hypoxic-ischemic brain damage in neonatal mice. Ann Transl Med. 2022;10:32. doi: 10.21037/atm-21-4958. PubMed PMID: 35282070; PubMed Central PMCID: PMCPMC8848430.
  33. Jafari A, Esmaeilzadeh Z, Khezri MR, Ghasemnejad-Berenji H, Pashapour S, Sadeghpour S, et al. An overview of possible pivotal mechanisms of Genistein as a potential phytochemical against SARS-CoV-2 infection: A hypothesis. J Food Biochem. 2022;46:e14345. doi: 10.1111/jfbc.14345. PubMed PMID: 35866873; PubMed Central PMCID: PMCPMC9350103.
  34. Li Y, Ou S, Liu Q, Gan L, Zhang L, Wang Y, et al. Genistein improves mitochondrial function and inflammatory in rats with diabetic nephropathy via inhibiting MAPK/NF-kappaB pathway. Acta Cir Bras. 2022;37:e370601. doi: 10.1590/acb370601. PubMed PMID: 35976278; PubMed Central PMCID: PMCPMC9377651.
  35. Shirvanian K, Vali R, Farkhondeh T, Abderam A, Aschner M, Samarghandian S. Genistein Effects on Various Human Disorders Mediated via Nrf2 Signaling. Curr Mol Med. 2024;24:40-50. doi: 10.2174/1566524023666221128162753. PubMed PMID: 36443970.
  36. Liu XJ, Bao HR, Zeng XL, Wei JM. Effects of resveratrol and genistein on nuclear factorkappaB, tumor necrosis factoralpha and matrix metalloproteinase9 in patients with chronic obstructive pulmonary disease. Mol Med Rep. 2016;13:4266-72. doi: 10.3892/mmr.2016.5057. PubMed PMID: 27035424; PubMed Central PMCID: PMCPMC4838123.
  37. Han JY, Jo A, Fukahori S, Tabor M, Kumar R, Yon DK, et al. Genotype-specific PAI-1 Regulation in Human Epithelial Cells and Mast Cells by Genistein. Journal of Allergy and Clinical Immunology. 2024;153:AB141. doi: 10.1016/j.jaci.2023.11.466.
  38. Cho S, Oh J, Han JY, Kim M, Cho J, Fukahori S, et al. Impact of soy isoflavones (genistein) on allergic asthma in epidemiologic and mouse models: national birth cohort in South Korea and murine model. Journal of Allergy and Clinical Immunology. 2024;153:AB20. doi: 10.1016/j.jaci.2023.11.085.
  39. Nazari-Khanamiri F, Ghasemnejad-Berenji M. Cellular and molecular mechanisms of genistein in prevention and treatment of diseases: An overview. J Food Biochem. 2021;45:e13972. doi: 10.1111/jfbc.13972. PubMed PMID: 34664285.
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