Login Register Cart 0
Generic placeholder image

Current Respiratory Medicine Reviews

Editor-in-Chief

ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

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

Pulmonary Fibrosis; Risk Factors and Molecular Triggers, Insight for Neo Therapeutic Approach

Author(s): Basheer Abdullah Marzoog*

Volume 18, Issue 4, 2022

Published on: 19 August, 2022

Page: [259 - 266] Pages: 8

DOI: 10.2174/1573398X18666220806124019

Price: $65

Abstract

Overactivation of the local pulmonary fibroblast induces hyperproduction of the extracellular matrix. A myriad of pathomorphological changes occur during lung fibrosis, including interalveolar space (interstitial) deposition due to proliferation and differentiation of resident fibroblasts, recruitment of circulating stem cells and epithelial-mesenchymal transition, highly reactive and hyperplastic alveolar epithelium. Currently, many endogenous and exogenous factors are believed to be associated with lung fibrosis development. However, pathogenetic treatment remains in the womb of development. Exploring the underlying pathophysiology is crucial for the successful development of pathogenetic treatment. Several molecules termed chemokines and cytokines have been found to induce lung fibrosis, such as IL-6, IL-1β, PDGFRα, TNF-α, GM-CSF, and IL-13. However, many others, such as IL-8, RANTES, IP-10, and MIG or lymphotactin, have an antifibrosis effect. However, the pathogenesis is multifactorial and involves dysregulation of the immune system, impaired cell-cell adhesion regulation mechanisms, and loss of DNA repair. The paper aimed to thoroughly address the potential risk factors and molecular triggers of lung fibrosis.

Keywords: Fibrosis, pathogenesis, pulmonary, pathogenetic therapy, angiogenesis, extracellular matrix, risk factor, molecular medicine, IL, cytokine.

« Previous Next »
Graphical Abstract

[1]
Bagnato, G.; Roberts, W.N.; Roman, J.; Gangemi, S. A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis. Eur. Respir. Rev., 2017, 26(144), 160125.
[http://dx.doi.org/10.1183/16000617.0125-2016] [PMID: 28515040]
[2]
Pollard, K.M. Silica, silicosis, and autoimmunity. Front. Immunol., 2016, 7, 97.
[http://dx.doi.org/10.3389/fimmu.2016.00097] [PMID: 27014276]
[3]
Barratt, S.L.; Creamer, A.; Hayton, C.; Chaudhuri, N. Idiopathic Pulmonary Fibrosis (IPF): An overview. J. Clin. Med., 2018, 7, 201.
[http://dx.doi.org/10.3390/jcm7080201]
[4]
Hobbs, S.; Chung, J.H.; Leb, J.; Kaproth-Joslin, K.; Lynch, D.A. Practical imaging interpretation in patients suspected of having idiopathic pulmonary fibrosis: Official recommendations from the radiology working group of the pulmonary fibrosis foundation. Radiol. Cardiothorac. Imaging, 2021, 3(1), e200279.
[http://dx.doi.org/10.1148/ryct.2021200279] [PMID: 33778653]
[5]
Song, J.W.; Do, K.H.; Kim, M.Y.; Jang, S.J.; Colby, T.V.; Kim, D.S. Pathologic and radiologic differences between idiopathic and collagen vascular disease-related usual interstitial pneumonia. Chest, 2009, 136(1), 23-30.
[http://dx.doi.org/10.1378/chest.08-2572] [PMID: 19255290]
[6]
Epstein Shochet, G.; Brook, E.; Bardenstein-Wald, B.; Shitrit, D. TGF-β pathway activation by idiopathic pulmonary fibrosis (IPF) fibroblast derived soluble factors is mediated by IL-6 trans-signaling. Respir. Res., 2020, 21(1), 56.
[http://dx.doi.org/10.1186/s12931-020-1319-0] [PMID: 32070329]
[7]
McGowan, S.E. The Formation of Pulmonary Alveoli Lung; Elsevier, 2014, pp. 65-84.
[http://dx.doi.org/10.1016/B978-0-12-799941-8.00004-3]
[8]
Kaunisto, J.; Salomaa, E.R.; Hodgson, U. Demographics and survival of patients with idiopathic pulmonary fibrosis in the FinnishIPF registry. ERJ Open Res., 2019, 5(3), 00170-02018.
[http://dx.doi.org/10.1183/23120541.00170-2018] [PMID: 31304177]
[9]
Maher, T.M.; Bendstrup, E.; Dron, L. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir. Res., 2021, 22(1), 197.
[http://dx.doi.org/10.1186/s12931-021-01791-z] [PMID: 34233665]
[10]
White, E.S. Lung extracellular matrix and fibroblast function. Ann. Am. Thorac. Soc., 2015, 12(Suppl. 1), S30-S33.
[http://dx.doi.org/10.1513/AnnalsATS.201406-240MG] [PMID: 25830832]
[11]
Blaauboer, M.E.; Boeijen, F.R.; Emson, C.L. Extracellular matrix proteins: A positive feedback loop in lung fibrosis? Matrix Biol., 2014, 34, 170-178.
[http://dx.doi.org/10.1016/j.matbio.2013.11.002] [PMID: 24291458]
[12]
Samarelli, A.V.; Tonelli, R.; Marchioni, A. Fibrotic idiopathic interstitial lung disease: The molecular and cellular key players. Int. J. Mol. Sci., 2021, 22(16), 8952.
[http://dx.doi.org/10.3390/ijms22168952] [PMID: 34445658]
[13]
Tan, W.; Wang, Y.; Chen, Y.; Chen, C. Cell tracing reveals the transdifferentiation fate of mouse lung epithelial cells during pulmonary fibrosis in vivo. Exp. Ther. Med., 2021, 22(4), 1188.
[http://dx.doi.org/10.3892/etm.2021.10622] [PMID: 34475978]
[14]
Huang, W.J.; Tang, X.X. Virus infection induced pulmonary fibrosis. J. Transl. Med., 2021, 19(1), 496.
[http://dx.doi.org/10.1186/s12967-021-03159-9] [PMID: 34876129]
[15]
Dinesh Babu, V.; Suresh Kumar, A.; Sudhandiran, G. Diosgenin inhibits TGF-β1/Smad signaling and regulates epithelial mesenchymal transition in experimental pulmonary fibrosis. Drug Chem. Toxicol., 2022, 45(3), 1264-1275.
[http://dx.doi.org/10.1080/01480545.2020.1814803] [PMID: 32924642]
[16]
Di Gregorio, J.; Robuffo, I.; Spalletta, S. The epithelial-to-mesenchymal transition as a possible therapeutic target in fibrotic disorders. Front. Cell Dev. Biol., 2020, 8, 607483.
[http://dx.doi.org/10.3389/fcell.2020.607483] [PMID: 33409282]
[17]
She, Y.X.; Yu, Q.Y.; Tang, X.X. Role of interleukins in the pathogenesis of pulmonary fibrosis. Cell Death Discov., 2021, 7, 1-10.
[http://dx.doi.org/10.1038/s41420-021-00437-9]
[18]
Raghu, G.; Remy-Jardin, M.; Myers, J.L. Diagnosis of idiopathic pulmonary fibrosis An official ATS/ERS/JRS/ALAT clinical practice guideline. Am. J. Respir. Crit. Care Med., 2018, 198(5), e44-e68.
[http://dx.doi.org/10.1164/rccm.201807-1255ST] [PMID: 30168753]
[19]
Stainer, A.; Faverio, P.; Busnelli, S. Molecular biomarkers in idiopathic pulmonary fibrosis: State of the art and future directions. Int. J. Mol. Sci., 2021, 22(12), 6255.
[http://dx.doi.org/10.3390/ijms22126255] [PMID: 34200784]
[20]
Choe, J.; Kwon, B.S.; Do, K.H.; Hwang, H.S.; Song, J.W.; Chae, E.J. Diagnostic and prognostic implications of 2018 guideline for the diagnosis of idiopathic pulmonary fibrosis in clinical practice. Sci. Rep., 2021, 11, 1-10.
[http://dx.doi.org/10.1038/s41598-021-95728-7]
[21]
Fraser, E.; Denney, L.; Antanaviciute, A. Multi-modal characterization of monocytes in idiopathic pulmonary fibrosis reveals a primed type I interferon immune phenotype. Front. Immunol., 2021, 12, 623430.
[http://dx.doi.org/10.3389/fimmu.2021.623430] [PMID: 33746960]
[22]
Scotton, C.J.; Chambers, R.C. Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest, 2007, 132(4), 1311-1321.
[http://dx.doi.org/10.1378/chest.06-2568] [PMID: 17934117]
[23]
Cottin, V. Significance of connective tissue diseases features in pulmonary fibrosis. Eur. Respir. Rev., 2013, 22(129), 273-280.
[http://dx.doi.org/10.1183/09059180.00003013] [PMID: 23997055]
[24]
Fingerlin, T.E.; Zhang, W.; Yang, I.V. Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia. BMC Genet., 2016, 17(1), 74.
[http://dx.doi.org/10.1186/s12863-016-0377-2] [PMID: 27266705]
[25]
Ellson, C.D.; Dunmore, R.; Hogaboam, C.M.; Sleeman, M.A.; Murray, L.A. Danger-associated molecular patterns and danger signals in idiopathic pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol., 2014, 51(2), 163-168.
[http://dx.doi.org/10.1165/rcmb.2013-0366TR] [PMID: 24749648]
[26]
Gu, X.; Wu, G.; Yao, Y. Intratracheal administration of mitochondrial DNA directly provokes lung inflammation through the TLR9-p38 MAPK pathway. Free Radic. Biol. Med., 2015, 83, 149-158.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.02.034] [PMID: 25772007]
[27]
Cesta, M.F.; Ryman-Rasmussen, J.P.; Wallace, D.G. Bacterial lipopolysaccharide enhances PDGF signaling and pulmonary fibrosis in rats exposed to carbon nanotubes. Am. J. Respir. Cell Mol. Biol., 2010, 43(2), 142-151.
[http://dx.doi.org/10.1165/rcmb.2009-0113OC] [PMID: 19738159]
[28]
Schaefer, L. Proteoglycans, key regulators of cell-matrix dynamics. Matrix Biol., 2014, 35, 1-2.
[http://dx.doi.org/10.1016/j.matbio.2014.05.001] [PMID: 24871042]
[29]
Karampitsakos, T.; Woolard, T.; Bouros, D.; Tzouvelekis, A. Toll-like receptors in the pathogenesis of pulmonary fibrosis. Eur. J. Pharmacol., 2017, 808, 35-43.
[http://dx.doi.org/10.1016/j.ejphar.2016.06.045] [PMID: 27364757]
[30]
Ge, X.; Arriazu, E.; Magdaleno, F. High mobility group box-1 drives fibrosis progression signaling via the receptor for advanced glycation end products in mice. Hepatology, 2018, 68(6), 2380-2404.
[http://dx.doi.org/10.1002/hep.30093] [PMID: 29774570]
[31]
Maeda, A.; Fadeel, B. Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals. Cell Death Dis., 2014, 5(7), e1312.
[http://dx.doi.org/10.1038/cddis.2014.277] [PMID: 24991764]
[32]
Bolourani, S.; Brenner, M.; Wang, P. The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis. J. Mol. Med. (Berl.), 2021, 99(10), 1373-1384.
[http://dx.doi.org/10.1007/s00109-021-02113-y] [PMID: 34258628]
[33]
Spagnolo, P.; Ryerson, C.J.; Putman, R. Early diagnosis of fibrotic interstitial lung disease: Challenges and opportunities. Lancet Respir. Med., 2021, 9(9), 1065-1076.
[http://dx.doi.org/10.1016/S2213-2600(21)00017-5] [PMID: 34331867]
[34]
Pallante, P.; Malapelle, U.; Nacchio, M. Liquid biopsy is a promising tool for genetic testing in idiopathic pulmonary fibrosis. Diagnostics (Basel), 2021, 11(7), 1202.
[http://dx.doi.org/10.3390/diagnostics11071202] [PMID: 34359285]
[35]
Akiyama, N.; Hozumi, H.; Isayama, T. Clinical significance of serum S100 calcium-binding protein A4 in idiopathic pulmonary fibrosis. Respirology, 2020, 25(7), 743-749.
[http://dx.doi.org/10.1111/resp.13707] [PMID: 31597225]
[36]
Kang, J.; Han, M.; Song, J.W. Antifibrotic treatment improves clinical outcomes in patients with idiopathic pulmonary fibrosis: A propensity score matching analysis. Sci. Rep., 2020, 10(1), 15620.
[http://dx.doi.org/10.1038/s41598-020-72607-1] [PMID: 32973215]
[37]
Flaherty, K.R.; Wells, A.U.; Cottin, V. Nintedanib in progressive fibrosing interstitial lung diseases. N. Engl. J. Med., 2019, 381(18), 1718-1727.
[http://dx.doi.org/10.1056/NEJMoa1908681] [PMID: 31566307]
[38]
King, TE; Bradford, wz; Castro-Bernardini, S; Fagan, EA; Glaspole, I A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. 2014, 370, 2083-2092.
[39]
Behr, J.; Nathan, S.D.; Wuyts, W.A. Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: A double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir. Med., 2021, 9(1), 85-95.
[http://dx.doi.org/10.1016/S2213-2600(20)30356-8] [PMID: 32822614]
[40]
Behr, J.; Prasse, A.; Kreuter, M. Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): A double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir. Med., 2021, 9(5), 476-486.
[http://dx.doi.org/10.1016/S2213-2600(20)30554-3] [PMID: 33798455]
[41]
Ishikawa, G.; Liu, A.; Herzog, E.L. Evolving perspectives on innate immune mechanisms of IPF. Front. Mol. Biosci., 2021, 8, 676569.
[http://dx.doi.org/10.3389/fmolb.2021.676569] [PMID: 34434962]
[42]
Taniguchi, H.; Ebina, M.; Kondoh, Y. Pirfenidone in idiopathic pulmonary fibrosis. Eur. Respir. J., 2010, 35(4), 821-829.
[http://dx.doi.org/10.1183/09031936.00005209] [PMID: 19996196]
[43]
Find, NHLBI https://www.nhlbi.nih.gov/research/clinical-trials?f%5B0%5D=disease_or_condition_name%3AIdiopathic
[44]
Raghu, G.; Brown, K.K.; Costabel, U. Treatment of idiopathic pulmonary fibrosis with etanercept: An exploratory, placebo-controlled trial. Am. J. Respir. Crit. Care Med., 2008, 178(9), 948-955.
[http://dx.doi.org/10.1164/rccm.200709-1446OC] [PMID: 18669816]
[45]
Ding, L; Wu, Z; Liu, T; Ullenbruch, M; Liu, J; Phan, SH Activation of stem cell Factor/c-Kit signaling pathway in pulmonary fibrosis. 2010, 181, A3536.
[http://dx.doi.org/10.1164/ajrccmconference.2010.181.1_MeetingAbstracts.A3536]
[46]
Datta, A.; Scotton, C.J.; Chambers, R.C. Novel therapeutic approaches for pulmonary fibrosis. Br. J. Pharmacol., 2011, 163(1), 141-172.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01247.x] [PMID: 21265830]
[47]
Liu, G.; Zhai, H.; Zhang, T. New therapeutic strategies for IPF: Based on the “phagocytosis-secretion-immunization” network regulation mechanism of pulmonary macrophages. Biomed. Pharmacother., 2019, 118, 109230.
[http://dx.doi.org/10.1016/j.biopha.2019.109230] [PMID: 31351434]
[48]
Wu, S.M.; Tsai, J.J.; Pan, H.C.; Arbiser, J.L.; Elia, L.; Sheu, M.L. Aggravation of pulmonary fibrosis after knocking down the aryl hydrocarbon receptor in the insulin-like growth factor 1 receptor pathway. Br. J. Pharmacol., 2022.
[http://dx.doi.org/10.1111/bph.15806] [PMID: 35083738]
[49]
Xu, Z.; Yuan, X.; Gao, Q.; Li, Y.; Li, M. Interleukin-38 overexpression prevents bleomycin-induced mouse pulmonary fibrosis. Naunyn Schmiedebergs Arch. Pharmacol., 2021, 394(2), 391-399.
[http://dx.doi.org/10.1007/s00210-020-01920-3] [PMID: 32577797]
[50]
Li, X.; Xie, M.; Lu, C. Design and synthesis of Leukotriene A4 hydrolase inhibitors to alleviate idiopathic pulmonary fibrosis and acute lung injury. Eur. J. Med. Chem., 2020, 203, 112614.
[http://dx.doi.org/10.1016/j.ejmech.2020.112614] [PMID: 32679453]
[51]
Jia, W.; Wang, Z.; Gao, C.; Wu, J.; Wu, Q. Trajectory modeling of endothelial-to-mesenchymal transition reveals galectin-3 as a mediator in pulmonary fibrosis. Cell Death Dis., 2021, 12(4), 327.
[http://dx.doi.org/10.1038/s41419-021-03603-0] [PMID: 33771973]
[52]
van Riet, S.; Ninaber, D.K.; Mikkers, H.M.M. In vitro modelling of alveolar repair at the air-liquid interface using alveolar epithelial cells derived from human induced pluripotent stem cells. Sci. Rep., 2020, 10(1), 5499.
[http://dx.doi.org/10.1038/s41598-020-62226-1] [PMID: 32218519]
[53]
Shiratori, T.; Tanaka, H.; Tabe, C. Effect of nintedanib on non-small cell lung cancer in a patient with idiopathic pulmonary fibrosis: A case report and literature review. Thorac. Cancer, 2020, 11(6), 1720-1723.
[http://dx.doi.org/10.1111/1759-7714.13437] [PMID: 32285615]
[54]
Guler, S.A.; Ebner, L.; Aubry-Beigelman, C. Pulmonary function and radiological features 4 months after COVID-19: First results from the national prospective observational Swiss COVID-19 lung study. Eur. Respir. J., 2021, 57(4), 2003690.
[http://dx.doi.org/10.1183/13993003.03690-2020] [PMID: 33419891]
[55]
Kiener, M.; Roldan, N.; Machahua, C. Human-based advanced in vitro approaches to investigate lung fibrosis and pulmonary effects of COVID-19. Front. Med. (Lausanne), 2021, 8, 644678.
[http://dx.doi.org/10.3389/fmed.2021.644678] [PMID: 34026781]
[56]
Zou, H.; Li, S.Q. Pulmonary fibrosis in critically ill patients with novel coronavirus pneumonia during the convalescent stage and a proposal for early intervention. Acta Pharmacol. Sin., 2021, 42(8), 1376-1378.
[http://dx.doi.org/10.1038/s41401-020-00566-4] [PMID: 33188277]
[57]
McDonald, L.T. Healing after COVID-19: Are survivors at risk for pulmonary fibrosis? Am. J. Physiol. Lung Cell. Mol. Physiol., 2021, 320(2), L257-L265.
[http://dx.doi.org/10.1152/ajplung.00238.2020] [PMID: 33355522]
[58]
Wiśniewska J, Sadowska A, Wójtowicz A, Słyszewska M, Szóstek-Mioduchowska A. Perspective on stem cell therapy in organ fibrosis: Animal models and human studies. Life (Basel), 2021, 11(10), 1068.
[http://dx.doi.org/10.3390/life11101068] [PMID: 34685439]
[59]
Marzoog, B.A.; Vlasova, T.I. Transcription factors in deriving β cell regeneration; A potential novel therapeutic target. Curr. Mol. Med., 2021, 22(5), 421-430.
[http://dx.doi.org/10.2174/1566524021666210712144638] [PMID: 34931980]
[60]
Marzoog, B.A.; Vlasova, T.I. https://www.eurekaselect.com/article/120948
[http://dx.doi.org/10.2174/1566524022666220216123650] [PMID: 35170408]
[61]
Noth, I.; Zhang, Y.; Ma, S.F. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: A genome-wide association study. Lancet Respir. Med., 2013, 1(4), 309-317.
[http://dx.doi.org/10.1016/S2213-2600(13)70045-6] [PMID: 24429156]
[62]
Allen, R.J.; Porte, J.; Braybrooke, R. Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: A genome-wide association study. Lancet Respir. Med., 2017, 5(11), 869-880.
[http://dx.doi.org/10.1016/S2213-2600(17)30387-9] [PMID: 29066090]
[63]
Wei, A.; Gao, Q.; Chen, F. Inhibition of DNA methylation de-represses peroxisome proliferator-activated receptor-γ and attenuates pulmonary fibrosis. Br. J. Pharmacol., 2022, 179(7), 1304-1318.
[http://dx.doi.org/10.1111/bph.15655] [PMID: 34378791]
[64]
Skeoch, S.; Weatherley, N.; Swift, A.J. Drug-Induced interstitial lung disease: A systematic review. J. Clin. Med., 2018, 7(10), 356.
[http://dx.doi.org/10.3390/jcm7100356] [PMID: 30326612]
[65]
Pardo, A.; Selman, M. The interplay of the genetic architecture, aging, and environmental factors in the pathogenesis of idiopathic pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol., 2021, 64(2), 163-172.
[http://dx.doi.org/10.1165/rcmb.2020-0373PS] [PMID: 32946290]
[66]
Hobbs, B.D.; Putman, R.K.; Araki, T. Overlap of genetic risk between interstitial lung abnormalities and idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med., 2019, 200(11), 1402-1413.
[http://dx.doi.org/10.1164/rccm.201903-0511OC] [PMID: 31339356]
[67]
Raslan, A.A.; Yoon, J.K. WNT signaling in lung repair and regeneration. Mol. Cells, 2020, 43(9), 774-783.
[http://dx.doi.org/10.14348/MOLCELLS.2020.0059] [PMID: 32807748]
[68]
Sivakumar, P.; Ammar, R.; Thompson, J.R. Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis. Respir. Res., 2021, 22(1), 273.
[http://dx.doi.org/10.1186/s12931-021-01860-3] [PMID: 34689792]

Rights & Permissions Print Cite
Article Metrics
1
© 2024 Bentham Science Publishers | Privacy Policy