The purpose of the study was to analyze literary sources on the study of modern views on information about the pathogenetic mechanisms of the formation of pulmonary fibrosis. Materials and methods. Analytical and bibliosemantic methods were used in the research. During the scientific search, 39 sources of modern domestic and foreign literature were reviewed and analyzed. Results and discussion. Pulmonary fibrosis is a heterogeneous group of chronic, progressive and incurable interstitial lung diseases characterized by scar formation and irreversible destruction of the lung parenchyma and is accompanied by disorders of elasticity and gas exchange in pathologically altered areas. The mechanism of development of pulmonary fibrosis is determined by its root causes. There are three distinct pathologic patterns of pulmonary fibrosis: usual interstitial pneumonia, fibrotic nonspecific interstitial pneumonia, and airway fibrosis. Their morphological differences are based on the distribution of fibrosis (diffuse or spotty) and anatomical location. The development of pulmonary fibrosis in most cases is a consequence of a previous acute inflammation of the lungs caused by various etiological factors, which in the case of untimely started or incorrectly selected treatment causes the deposition of fibrous tissue in the lungs. It is believed that the appearance and subsequent progression of pulmonary fibrosis can be attributed to reparative processes after repeated injuries of alveolar epithelial cells in response to various stimuli, including injuries. Loss of function or reduction in the number of alveolar epithelial cells can lead to improper repair of the lung parenchyma, which can lead to fibrosis. Various cytokines such as transforming growth factor-β1, tumor necrosis factor-α, and platelet-derived growth factor can be released when alveolar epithelial cells are damaged. These cytokines can promote the accumulation of fibroblasts. In addition to the cytokine response, the lung’s response to injury includes the stimulation of myofibroblasts, which when activated serve as the primary collagen-producing cell. This leads to massive deposition of collagen and subsequently affects the normal structure and function of lung tissue. Conclusion. Pulmonary fibrosis is a progressive lung disease that leads to morpho-functional restructuring of lung tissue. In the course of the work, the presence of three models of the development of pulmonary fibrosis were analyzed. Despite the long history of study and good coverage of the problem in the scientific literature, currently the mechanisms of formation of pulmonary fibrosis remain insufficiently studied

Keywords: pulmonary fibrosis, pneumonia, mechanisms

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1. Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet. 2017;389:1941-1952. PMID: 28365056. https://doi.org/10.1016/S0140-6736(17)30866-8
2. Martinez F, Collard H, Pardo A, Raghu G, Richeldi L, Selman M, et al. Idiopathic pulmonary fibrosis. Nat Rev Dis Primers. 2017;3:170-174. PMID: 29052582. https://doi.org/10.1038/nrdp.2017.74
3. Wolters PJ, Blackwell TS, Eickelberg O, Loyd JE, Kaminski N, Jenkins G, et al. Time for a change: Is idiopathic pulmonary fibrosis still idiopathic and only fibrotic? Lancet Respir Med. 2018;6:154-160. PMID: 29413083. https://doi.org/10.1016/S2213-2600(18)30007-9
4. Sharif R. Overview of idiopathic pulmonary fibrosis (IPF) and evidence-based guidelines. Am J Manag Care. 2017;23(11 Suppl):176-182. PMID: 28978212
5. Krauss E, Gehrken G, Drakopanagiotakis F, Tello S, Ruth CD, Maurer O, et al. Clinical characteristics of patients with familial idiopathic pulmonary fibrosis (f-IPF). BMC Pulmon Med. 2019;19(1):130. PMID: 31319833. PMCID: PMC6637501. https://doi.org/10.1186/s12890-019-0895-6
6. Lederer DJ, Martinez FG. Idiopathic pulmonary fibrosis. New Eng J Med. 2018;378(19):1811-1823. PMID: 29742380. https://doi.org/10.1056/NEJMra1705751
7. Distler JHW, Gyorfi AH, Ramanujam M, Whitfield ML, Konigshoff M, Lafyatis R. Shared and distinct mechanisms of fibrosis. Nat Rev Rheumatol. 2019;15:705-30. PMID: 31712723. https://doi.org/10.1038/s41584-019-0322-7
8. Shi J, Zhou L, Wang X, Du J, Jiang M, Song Z, et al. KLF2 attenuates bleomycin-induced pulmonary fibrosis and inflammation with regulation of AP-1. Biochem Biophys Res Commun. 2018;495(1):20-26. PMID: 29079188. https://doi.org/10.1016/j.bbrc.2017.10.114
9. Parimon T, Yao C, Stripp BR, Noble PW, Chen P. Alveolar epithelial type II cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis. Int J Mol Sci. 2020;21:2269. PMID: 32218238. PMCID: PMC7177323. https://doi.org/10.3390/ijms21072269
10. Lee CM, He CH, Park JW, Lee JH, Kamle S, Ma B, et al. Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Sci Alliance. 2019;2(3):e201900350. PMID: 31085559. PMCID: PMC6516052. https://doi.org/10.26508/lsa.201900350
11. Hou J, Ma T, Cao H, Chen Y, Wang C, Chen X, et al. TNF-α-induced NF-κB activation promotes myofibroblast differentiation of LR-MSCs and exacerbates bleomycin-induced pulmonary fibrosis. J Cell Physiol. 2018 Mar;233(3):2409-2419. PMID: 28731277. https://doi.org/10.1002/jcp.26112
12. Kishi M, Aono Y, Sato S, Koyama K, Azuma M, Abe S, et al. Blockade of platelet-derived growth factor receptor-β, not receptor-α ameliorates bleomycin-induced pulmonary fibrosis in mice. PLoS One. 2018;13(12):e0209786. PMID: 30596712. PMCID: PMC6312310. https://doi.org/10.1371/journal.pone.0209786
13. Saito A, Horie M, Nagase T. TGF-β signaling in lung health and disease. Int J Mol Sci. 2018;19(8):2460. PMID: 30127261. PMCID: PMC6121238. https://doi.org/10.3390/ijms19082460
14. Muthuramalingam K, Cho M, Kim Y. Cellular senescence and EMT crosstalk in bleomycin-induced pathogenesis of pulmonary fibrosis-an in vitro analysis. Cell Biol Int. 2019;44(2):477-487. PMID: 31631444. https://doi.org/10.1002/cbin.11248
15. Zhang HX, Li YN, Wang XL, Ye CL, Zhu XY, Li HP, et al. Probucol ameliorates EMT and lung fibrosis through restoration of SIRT3 expression. Pulmon Pharmacol Ther. 2019;57:101803. PMID: 31085231. https://doi.org/10.1016/j.pupt.2019.101803
16. Wei P, Xie Y, Abel PW, Huang Y, Ma Q, Li L, t al. Transforming growth factor (TGF)-β1-induced miR-133a inhibits myofibroblast differentiation and pulmonary fibrosis. Cell Death Dis. 2019;10:670. PMID: 31511493. PMCID: PMC6739313. https://doi.org/10.1038/s41419-019-1873-x
17. Li H, Zhao C, Tian Y, Lu J, Zhang G, Liang S, et al. Src family kinases and pulmonary fibrosis: A review. Biomed Pharmacother. 2020;127:110183. PMID: 32388241. https://doi.org/10.1016/j.biopha.2020.110183
18. Xie N, Tan Z, Banerjee S, Cui H, Ge J, Liu RM, et al. Glycolytic reprogramming in myofibroblast differentiation and lung fibrosis. Am J Respir Crit Care Med. 2015 Dec 15;192(12):1462-74. PMID: 26284610. PMCID: PMC4731722. https://doi.org/10.1164/rccm.201504-0780OC
19. Gu L, Larson-Casey JL, Andrabi SA, Lee JH, Meza-Perez S, Randall TD, et al. Mitochondrial calcium uniporter regulates PGC-1alpha expression to mediate metabolic reprogramming in pulmonary fibrosis. Redox Biol. 2019;26:101307. PMID: 31473487. PMCID: PMC6831865. https://doi.org/10.1016/j.redox.2019.101307
20. Carraway MS, Suliman HB, Kliment C, Welty-Wolf KE, Oury TD, Piantadosi CA. Mitochondrial biogenesis in the pulmonary vasculature during inhalational lung injury and fibrosis. Antioxidants Redox Signal. 2008;10:269-275. PMID: 17999632. PMCID: PMC2268979. https://doi.org/10.1089/ars.2007.1910
21. Lehmann M, Buhl L, Alsafadi HN, Klee S, Hermann S, Mutze K, et al. Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis. Respir Res. 2018;19(1):175. PMID: 30219058. PMCID: PMC6138909. https://doi.org/10.1186/s12931-018-0876-y
22. Zhang Y, Guan L, Zheng Y, Mao L, Li S, Zhao J. Extracellular histones promote pulmonary fibrosis in patients with coal workers' pneumoconiosis. J Occup Environ Med. 2019;61(2):89-95. PMID: 30308624. https://doi.org/10.1097/JOM.0000000000001473
23. Li Y, Gao Q, Xu K, Peng X, Yuan X, Jiang W, et al. Interleukin-37 attenuates bleomycin-induced pulmonary inflammation and fibrosis in mice. Inflammation. 2018 Oct;41(5):1772-1779. PMID: 29956068. https://doi.org/10.1007/s10753-018-0820-9
24. Chainy GBN, Sahoo DK. Hormones and oxidative stress: an overview. Free Radic Res. 2020 Jan;54(1):1-26. PMID: 31868060. https://doi.org/10.1080/10715762.2019.1702656
25. Yang S, Lian G. ROS and diseases: role in metabolism and energy supply. Mol Cell Biochem. 2020 Apr;467(1-2):1-12. PMID: 31813106. PMCID: PMC7089381. https://doi.org/10.1007/s11010-019-03667-9
26. Hosseinzadeh A, Javad-Moosavi SA, Reiter RJ, Yarahmadi R, Ghaznavi H, Mehrzadi S. Oxidative/nitrosative stress, autophagy and apoptosis as therapeutic targets of melatonin in idiopathic pulmonary fibrosis. Expert Opin Ther Targets. 2018 Dec;22(12):1049-1061. PMID: 30445883. https://doi.org/10.1080/14728222.2018.1541318
27. Mirzaee S, Mansouri E, Shirani M, Zeinvand-Lorestani M, Khodayar MJ. Diosmin ameliorative effects on oxidative stress and fibrosis in paraquat-induced lung injury in mice. Environ Sci Pollut Res Int. 2019 Dec;26(36):36468-36477. PMID: 31732951. https://doi.org/10.1007/s11356-019-06572-2
28. Anathy V, Lahue KG, Chapman DG, Chia SB, Casey DT, Aboushousha R, et al. Reducing protein oxidation reverses lung fibrosis. Nat Med. 2018 Aug;24(8):1128-1135. PMID: 29988126. PMCID: PMC6204256. https://doi.org/10.1038/s41591-018-0090-y
29. Yan B, Ma Z, Shi S, Hu Y, Ma T, Rong G, et al. Sulforaphane prevents bleomycin induced pulmonary fibrosis in mice by inhibiting oxidative stress via nuclear factor erythroid 2-related factor-2 activation. Mol Med Rep. 2017 Jun;15(6):4005-4014. PMID: 28487960. PMCID: PMC5436151. https://doi.org/10.3892/mmr.2017.6546
30. Leslie KO. Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung: a unifying hypothesis regarding etiology and pathogenesis. Arch Pathol Lab Med. 2012;136(6):591-600. PMID: 22136526. https://doi.org/10.5858/arpa.2011-0511-OA
31. Poletti V, Romagnoli M, Piciucchi S, Chilosi M. Current status of idiopathic nonspecific interstitial pneumonia. Semin Respir Crit Care Med. 2012;33(5):440-449. PMID: 23001799. https://doi.org/10.1055/s-0032-1325155
32. Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, Bois RM, et al. ERS/ATS Task Force on Undifferentiated Forms of CTD-ILD. An Official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015;46(4):976-987. PMID: 26160873. https://doi.org/10.1183/13993003.00150-2015
33. Kuranishi LT, Leslie KO, Ferreira RG, Coletta EAN, Storrer KM, Soares MR, et al. Airway-centered interstitial fibrosis: etiology, clinical findings and prognosis. Respir Res. 2015;16:55. PMID: 25956471. PMCID: PMC4429710. https://doi.org/10.1186/s12931-015-0213-7
34. Valeyre D, Duchemann B, Nunes H, Uzunhan Y, Annesi-Maesano I. Interstitial lung diseases. In: Respiratory Epidemiology. Eds by Welte T, Annesi-Maesano I, Viegi G, Lundback B. 2014. Vol 65 of ERS Monograph, Chapter 6: ERS. https://doi.org/10.1183/2312508X.10012913
35. Strachunski AS, Bilousov YuB, Kozlov SM, Eds. Antibacterial therapy. 2000. 190 p.
36. Tsarkova LM. Chronic pneumonia. In: Diseases of the respiratory organs. 2000. p. 441-449.
37. Ostrovsʹkyy MM. Rolʹ system surfaktantu lehenʹ ta interleykiniv u protsesi formuvannya zatyazhnoho perebihu pnevmoniy [The role of lung surfactant systems and interleukins in the formation of a protracted course of pneumonia]. Pulmon J. 2004;2:23-25. [Ukrainian]
38. Neyko YeM, Ostrovsʹkyy MM. Deyaki imunolohichni kryteriyi zvychaynoho ta zatyazhnoho perebihu pnevmoniy [Some immunological criteria of normal and prolonged course of pneumonia]. Ukr Pulmon J. 2002;2:32-34. [Ukrainian]
39. Delʹtsova OI, Ostrovsʹkyy MM. Morfolohichna kharakterystyka lehenʹ u khvorykh na nehospitalʹnu pnevmoniyu iz zvychaynym ta zatyazhnym perebihom riznykh form tyazhkosti [Morphological characteristics of the lungs in patients with community-acquired pneumonia with the usual and protracted course of various forms of severity]. Halytskyy Likarsʹkyy Visnyk. 2004;1:45-48. [Ukrainian]