Role of Epigenetic Mechanisms in Lung Fibrosis: Therapeutic Opportunities and Challenges

[{“box”:0,”content”:”[if 992 equals=”Open Access”]n

n

n

n

Open Access

nn

n

n[/if 992]n

n

Year : August 12, 2024 at 3:03 pm | [if 1553 equals=””] Volume : [else] Volume :[/if 1553] | [if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424] : | Page : –

n

n

n

n

n

n

By

n

[foreach 286]n

vector

n

n

Shivangi, Jai Prakash Muyal,

n

    n t

  • n

n

n[/foreach]

n

n[if 2099 not_equal=”Yes”]n

    [foreach 286] [if 1175 not_equal=””]n t

  1. Assistant Professor, Assistant Professor Department of Biotechnology, School of Biotechnology, Gautam Buddha University, Department of Biotechnology, School of Biotechnology, Gautam Buddha University Uttar Pradesh, Uttar Pradesh India, India

    2. n[/if 1175][/foreach]

n[/if 2099][if 2099 equals=”Yes”][/if 2099]n

n

Abstract

nLung fibrosis poses a serious risk to one’s health since it might result in respiratory failure due to an abnormal accumulation of fibrotic tissue in the lungs. Epigenetic mechanisms, such as histone changes, DNA methylation, and non-coding RNAs, closely control gene expression patterns and cellular processes associated with lung fibrosis. Anomalies in DNA methylation patterns connected to changes in gene expression profiles and disturbances in fibrotic signalling pathways are potential targets for diagnosis and treatment in fibrotic lungs. A portion of the abnormal gene expression patterns and decreased cellular activity observed in fibrotic lungs can be explained by hepatocellular dysregulation. Non-coding RNAs have an impact on crucial signalling pathways that cause lung fibrosis to develop. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two examples of these routes. Collaboration between medical professionals, researchers, regulators, and the advancement of pulmonary fibrosis precision medicine therapies depends on industry actors. Recent developments in the CRISPR-Cas9 system have enabled epigenetic editing. This study examines the benefits and drawbacks of using these modifications for medical treatment. A few concerns need to be fixed before epigenetic therapies may be used effectively in clinical settings. Delivery, specificity, off-target repercussions and morality are some of these challenges. The goal of this review is to enhance patient outcomes and quality of life by investigating the intricate relationship between epigenetic modifications and the biology of lung fibrosis.

n

n

n

Keywords: Lung fibrosis, Epigenetics, DNA methylation, Histone modifications, non-coding RNAs, Therapeutic intervention.

n[if 424 equals=”Regular Issue”][This article belongs to Research & Reviews : A Journal of Medical Science and Technology(rrjomst)]

n

[/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue under section in Research & Reviews : A Journal of Medical Science and Technology(rrjomst)][/if 424][if 424 equals=”Conference”]This article belongs to Conference [/if 424]

n

n

n

How to cite this article: Shivangi, Jai Prakash Muyal. Role of Epigenetic Mechanisms in Lung Fibrosis: Therapeutic Opportunities and Challenges. Research & Reviews : A Journal of Medical Science and Technology. August 12, 2024; ():-.

n

How to cite this URL: Shivangi, Jai Prakash Muyal. Role of Epigenetic Mechanisms in Lung Fibrosis: Therapeutic Opportunities and Challenges. Research & Reviews : A Journal of Medical Science and Technology. August 12, 2024; ():-. Available from: https://journals.stmjournals.com/rrjomst/article=August 12, 2024/view=0

nn[if 992 equals=”Open Access”] Full Text PDF Download[/if 992] n

n[if 992 not_equal=’Open Access’] [/if 992]n

nn

nn[if 379 not_equal=””]n

Browse Figures

n

n

[foreach 379]n

n[/foreach]n

n

n

n[/if 379]n

n

References

n[if 1104 equals=””]n

  1. Murtha LA, Schuliga MJ, Mabotuwana NS, Hardy SA, Waters DW, Burgess JK, Knight DA, Boyle AJ. The processes and mechanisms of cardiac and pulmonary fibrosis. Frontiers in physiology. 2017 Oct 12;8:777.
  2. Lee JY, Yoon SH, Goo JM, Park J, Lee JH. Association between body fat decrease during the first year after diagnosis and the prognosis of idiopathic pulmonary fibrosis: CT-based body composition analysis. Respir Res. 2024;25(1). doi:10.1186/S12931-024-02712-6
  3. Savin IA, Zenkova MA, Sen’kova A V. Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches. Int J Mol Sci. 2022;23(23). doi:10.3390/ijms232314959
  4. Macneal K, Schwartz DA. The genetic and environmental causes of pulmonary fibrosis. Proceedings of the American Thoracic Society. 2012 Jul 15;9(3):120-5.doi:10.1513/pats.201112-055AW
  5. Gandhi S, Tonelli R, Murray M, Samarelli AV, Spagnolo P. Environmental Causes of Idiopathic Pulmonary Fibrosis. International Journal of Molecular Sciences. 2023 Nov 18;24(22):16481. doi:10.3390/IJMS242216481
  6. Rivera-Ortega P, Molina-Molina M. Interstitial lung diseases in developing countries. Ann Glob Health. 2019;85(1). doi:10.5334/aogh.2414
  7. Ye Z, Hu Y. TGF-β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review). Int J Mol Med. 2021;48(1). doi:10.3892/ijmm.2021.4965
  8. Barros A, Oldham J, Noth I. Genetics of Idiopathic Pulmonary Fibrosis. American Journal of the Medical Sciences. 2019;357(5). doi:10.1016/j.amjms.2019.02.009
  9. Yang I V., Schwartz DA. Epigenetics of idiopathic pulmonary fibrosis. Translational Research. 2015;165(1). doi:10.1016/j.trsl.2014.03.011
  10. Raghu G, Collard HR, Egan JJ, et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic pulmonary fibrosis: Evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6). doi:10.1164/rccm.2009-040GL
  11. Wylam ME, Sathish V, VanOosten SK, et al. Mechanisms of cigarette smoke effects on human airway smooth muscle. PLoS One. 2015;10(6). doi:10.1371/journal.pone.0128778
  12. Redington AE. Airway fibrosis in asthma: Mechanisms, consequences, and potential for therapeutic intervention. Monaldi Archives for Chest Disease. 2000;55(4).
  13. Lennartsson A, Ekwall K. Histone modification patterns and epigenetic codes. Biochim Biophys Acta Gen Subj. 2009;1790(9). doi:10.1016/j.bbagen.2008.12.006
  14. Ghavifekr Fakhr M, Farshdousti Hagh M, Shanehbandi D, Baradaran B. DNA Methylation Pattern as Important Epigenetic Criterion in Cancer. Genet Res Int. 2013;2013. doi:10.1155/2013/317569
  15. Peschansky VJ, Wahlestedt C. Non-coding RNAs as direct and indirect modulators of epigenetic regulation. Epigenetics. 2014;9(1). doi:10.4161/epi.27473
  16. Yang I V., Schwartz DA. Epigenetic mechanisms and the development of asthma. Journal of Allergy and Clinical Immunology. 2012;130(6). doi: 10.1016/j.jaci.2012.07.052
  17. Velagacherla V, Mehta CH, Nayak Y, Nayak UY. Molecular pathways and role of epigenetics in the idiopathic pulmonary fibrosis. Life Sci. 2022;291. doi:10.1016/j.lfs.2021.120283
  18. Boucherat O, Vitry G, Trinh I, Paulin R, Provencher S, Bonnet S. The cancer theory of pulmonary arterial hypertension. Pulm Circ. 2017;7(2). doi:10.1177/2045893217701438
  19. Selman M, López-Otín C, Pardo A. Age-driven developmental drift in the pathogenesis of idiopathic pulmonary fibrosis. European Respiratory Journal. 2016;48(2). doi:10.1183/13993003.00398-2016
  20. Sehgal M, Jakhete SM, Manekar AG, Sasikumar S. Specific epigenetic regulators serve as potential therapeutic targets in idiopathic pulmonary fibrosis. Heliyon. 2022;8(8). doi:10.1016/j.heliyon.2022.e09773
  21. Ligresti G, Raslan AA, Hong J, Caporarello N, Confalonieri M, Huang SK. Mesenchymal cells in the Lung: Evolving concepts and their role in fibrosis. Gene. 2023 Apr 5;859:147142. doi:10.1016/j.gene.2022.147142
  22. Xue T, Qiu X, Liu H, Gan C, Tan Z, Xie Y, Wang Y, Ye T. Epigenetic regulation in fibrosis progress. Pharmacological research. 2021 Nov 1;173:105910. doi:10.1016/j.phrs.2021.105910
  23. Jeltsch A, Broche J, Bashtrykov P. Molecular processes connecting DNA methylation patterns with DNA methyltransferases and histone modifications in mammalian genomes. Genes (Basel). 2018;9(11). doi:10.3390/genes9110566
  24. Liu Y, Leng P, Liu Y, Guo J, Zhou H. Crosstalk between Methylation and ncRNAs in Breast Cancer: Therapeutic and Diagnostic Implications. Int J Mol Sci. 2022;23(24). doi:10.3390/ijms232415759
  25. Lu J, Huang Y, Zhang X, Xu Y, Nie S. Noncoding RNAs involved in DNA methylation and histone methylation, and acetylation in diabetic vascular complications. Pharmacol Res. 2021;170. doi:10.1016/j.phrs.2021.105520
  26. Sanders YY, Ambalavanan N, Halloran B, et al. Altered DNA methylation profile in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012;186(6). doi:10.1164/rccm.201201-0077OC
  27. Neary R, Watson CJ, Baugh JA. Epigenetics and the overhealing wound: The role of DNA methylation in fibrosis. Fibrogenesis Tissue Repair. 2015;8(1). doi:10.1186/s13069-015-0035-8
  28. Yang I V., Pedersen BS, Rabinovich E, et al. Relationship of DNA methylation and gene expression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2014;190(11). doi:10.1164/rccm.201408-1452OC
  29. Duan J, Zhong B, Fan Z, et al. DNA methylation in pulmonary fibrosis and lung cancer. Expert Rev Respir Med. 2022;16(5). doi:10.1080/17476348.2022.2085091
  30. Brown TA, Lee JW, Holian A, et al. Alterations in DNA methylation corresponding with lung inflammation and as a biomarker for disease development after MWCNT exposure. Nanotoxicology. 2016;10(4). doi:10.3109/17435390.2015.1078852
  31. Jiang Y, Fu J, Du J, et al. DNA methylation alterations and their potential influence on macrophage in periodontitis. Oral Dis. 2022;28(2). doi:10.1111/odi.13654
  32. Jones PA. Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7). doi:10.1038/nrg3230
  33. Razin A, Riggs AD. DNA Methylation and gene function. Science (1979). 1980;210(4470). doi:10.1126/science.6254144
  34. Zhang X, Hu M, Lyu X, Li C, Thannickal VJ, Sanders YY. DNA methylation regulated gene expression in organ fibrosis. Biochim Biophys Acta Mol Basis Dis. 2017;1863(9). doi:10.1016/j.bbadis.2017.05.010
  35. Marzoog BA. Local Lung Fibroblast Autophagy in the Context of Lung Fibrosis Pathogenesis. Curr Respir Med Rev. 2022;19(1). doi:10.2174/1573398×19666221130141600
  36. Garner I. DNA methylation in lung fibroblasts and its role in pulmonary fibrosis. Doctoral thesis, UCL (University College London) . Published online April 28, 2016. https://discovery.ucl.ac.uk/id/eprint/1478244/
  37. Limjunyawong N, Mitzner W, Horton MR. A mouse model of chronic idiopathic pulmonary fibrosis. Physiol Rep. 2014;2(2). doi:10.1002/phy2.249
  38. Smith ZD, Meissner A. DNA methylation: Roles in mammalian development. Nat Rev Genet. 2013;14(3). doi:10.1038/nrg3354
  39. Comer BS, Ba M, Singer CA, Gerthoffer WT. Epigenetic targets for novel therapies of lung diseases. Pharmacol Ther. 2015;147. doi:10.1016/j.pharmthera.2014.11.006
  40. Rosas IO, Yang I V. The promise of epigenetic therapies in treatment of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2013;187(4). doi:10.1164/rccm.201212-2272ED
  41. Bhan A, Deb P, Mandal SS. Epigenetic code: histone modification, gene regulation, and chromatin dynamics. Gene regulation, epigenetics and hormone signaling. 2017 Jul 12:29-58.
  42. Liu Y, Li H, Xiao T, Lu Q. Epigenetics in immune-mediated pulmonary diseases. Clin Rev Allergy Immunol. 2013;45(3). doi:10.1007/s12016-013-8398-3
  43. Kouzarides T. Chromatin Modifications and Their Function. Cell. 2007;128(4). doi:10.1016/j.cell.2007.02.005
  44. Li X, Feng C, Peng S. Epigenetics alternation in lung fibrosis and lung cancer. Front Cell Dev Biol. 2022;10. doi:10.3389/fcell.2022.1060201
  45. Korfei M, Mahavadi P, Guenther A. Targeting Histone Deacetylases in Idiopathic Pulmonary Fibrosis: A Future Therapeutic Option. Cells. 2022;11(10). doi:10.3390/cells11101626
  46. Hadjicharalambous MR, Lindsay MA. Idiopathic pulmonary fibrosis: Pathogenesis and the emerging role of long non-coding RNAs. Int J Mol Sci. 2020;21(2). doi:10.3390/ijms21020524
  47. Omote N, Sauler M. Non-coding RNAs as Regulators of Cellular Senescence in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease. Front Med (Lausanne). 2020;7. doi:10.3389/fmed.2020.603047
  48. Kopp F, Mendell JT. Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell. 2018;172(3). doi:10.1016/j.cell.2018.01.011
  49. Rajasekaran S, Rajaguru P, Sudhakar Gandhi PS. MicroRNAs as potential targets for progressive pulmonary fibrosis. Front Pharmacol. 2015;6(NOV). doi:10.3389/fphar.2015.00254
  50. Li H, Zhao X, Shan H, Liang H. MicroRNAs in idiopathic pulmonary fibrosis: involvement in pathogenesis and potential use in diagnosis and therapeutics. Acta Pharm Sin B. 2016;6(6). doi:10.1016/j.apsb.2016.06.010
  51. Saadat S, Noureddini M, Mahjoubin-Tehran M, et al. Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players. Front Cardiovasc Med. 2021;7. doi:10.3389/fcvm.2020.588347
  52. Bowen T, Jenkins RH, Fraser DJ. MicroRNAs, transforming growth factor beta-1, and tissue fibrosis. Journal of Pathology. 2013;229(2). doi:10.1002/path.4119
  53. Foulks JM, Parnell KM, Nix RN, et al. Epigenetic Drug Discovery:Targeting DNA Methyltransferases. J Biomol Screen. 2012;17(1):2-17. doi: 10.1177/1087057111421212/ASSET/IMAGES/LARGE/10.1177_1087057111421212-FIG3.JPEG
  54. Yue Ren, Qinsheng Sun, Zigao Yuan, Yuyang Jiang. Combined inhibition of HDAC and DNMT1 induces p85α/MEK-mediated cell cycle arrest by dual target inhibitor 208 in U937 cells. Chinese Chemical Letters 2019; 30(6), 1233-1236.
  55. Nie L, Liu Y, Zhang B, Zhao J. Application of Histone Deacetylase Inhibitors in Renal Interstitial Fibrosis. Kidney Diseases. 2020;6(4). doi:10.1159/000505295
  56. Lyu X, Hu M, Peng J, Zhang X, Sanders YY. HDAC inhibitors as antifibrotic drugs in cardiac and pulmonary fibrosis. Ther Adv Chronic Dis. 2019;10. doi:10.1177/2040622319862697
  57. Kang JG, Park JS, Ko JH, Kim YS. Regulation of gene expression by altered promoter methylation using a CRISPR/Cas9-mediated epigenetic editing system. Sci Rep. 2019;9(1). doi:10.1038/s41598-019-48130-3
  58. Effendi WI, Nagano T. Epigenetics Approaches toward Precision Medicine for Idiopathic Pulmonary Fibrosis: Focus on DNA Methylation. Biomedicines. 2023;11(4). doi:10.3390/biomedicines11041047
  59. Pflueger C, Swain T, Lister R. Harnessing targeted DNA methylation and demethylation using dCas9. Essays Biochem. 2019;63(6). doi:10.1042/EBC20190029
  60. Hilton IB, D’Ippolito AM, Vockley CM, et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol. 2015;33(5). doi:10.1038/nbt.3199

nn[/if 1104][if 1104 not_equal=””]n

    [foreach 1102]n t

  1. [if 1106 equals=””], [/if 1106][if 1106 not_equal=””],[/if 1106]

    2. n[/foreach]

n[/if 1104]

nn

nn[if 1114 equals=”Yes”]n

n[/if 1114]

n

n

[if 424 not_equal=””][else]Ahead of Print[/if 424] Subscription Review Article

n

n

[if 2146 equals=”Yes”][/if 2146][if 2146 not_equal=”Yes”][/if 2146]n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n[if 1748 not_equal=””]

[else]

[/if 1748]n

n

n

Volume
[if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424]
Received April 2, 2024
Accepted April 23, 2024
Published August 12, 2024

n

n

221

n

n

n

n nfunction myFunction2() {nvar x = document.getElementById(“browsefigure”);nif (x.style.display === “block”) {nx.style.display = “none”;n}nelse { x.style.display = “Block”; }n}ndocument.querySelector(“.prevBtn”).addEventListener(“click”, () => {nchangeSlides(-1);n});ndocument.querySelector(“.nextBtn”).addEventListener(“click”, () => {nchangeSlides(1);n});nvar slideIndex = 1;nshowSlides(slideIndex);nfunction changeSlides(n) {nshowSlides((slideIndex += n));n}nfunction currentSlide(n) {nshowSlides((slideIndex = n));n}nfunction showSlides(n) {nvar i;nvar slides = document.getElementsByClassName(“Slide”);nvar dots = document.getElementsByClassName(“Navdot”);nif (n > slides.length) { slideIndex = 1; }nif (n (item.style.display = “none”));nArray.from(dots).forEach(nitem => (item.className = item.className.replace(” selected”, “”))n);nslides[slideIndex – 1].style.display = “block”;ndots[slideIndex – 1].className += ” selected”;n}n”}]