Experimental Models of Pulmonary Fibrosis and their Translational Potential

Adamcakova Jana; Palova Romana; Mokra Daniela

doi:10.2478/acm-2019-0013

Abstract

Pulmonary fibrosis, represented mainly by idiopathic pulmonary fibrosis, develops chronic and progressive changes in lung parenchyma with high mortality and limited therapeutic options. The aim of this review was to summarize the most common experimental models used in the research of pulmonary fibrosis. Lung damage associated with development of pulmonary fibrosis can be caused by irradiation or by instillation of bleomycin, fluorescein isothiocyanate (FITC), silicon dioxide (silica), asbestos, etc. This article reviews the characteristics of the most frequently used animal models of fibrosis, including the limitations of their use. Although none of the used animal models resembles completely the changes in human pulmonary fibrosis, similarities between them allow preclinical testing of novel treatment approaches or their combinations in the laboratory conditions before their use in the clinical practice.

References

1. Moore BB, Hogaboam CM. Animal model of human lung disease. Am J Physiol Lung Cell Mol Physiol 2008; 294: 152-60.
Search in Google Scholar Back to article
2. Fujimoto H, Kobayashi T, Azuma A. Idiopathic Pulmonary Fibrosis: treatment and prognosis. Clin Med Insights Circ Respir Pulm Med 2016; 9: 179-85.
Search in Google Scholar Back to article
3. Carrington R, Jordan S, Pitchford SC, Page CP. Use of animal models in IPF research. Pulm Pharmacol Ther 2018; 51: 73-8.
Search in Google Scholar Back to article
4. Sanchez VC, Pietruska JR, Miselis NR, et al. Biopersistence and potential adverse health impacts of fibrous nanomaterials: what have we learned from asbestos? Wiley Interdiscip Rev Nanomed Nanobiotechnol 2009; 1: 511-29.
Search in Google Scholar Back to article
5. Takita T, Muraoka Y, Nakatani T, et al. Metal-complex of bleomycin and its implication for the mechanism of bleomycin action. J Antibiot 1978; 31: 1073-7.
Search in Google Scholar Back to article
6. Della Latta V, Cecchettini A, Del Ry S, et al. Bleomycin in the setting of lung fibrosis induction: from biological mechanisms to counteractions. Pharmacol Res 2015; 97: 122-30.
Search in Google Scholar Back to article
7. Claussen CA, Long EC. Nucleic Acid recognition by metal complexes of bleomycin. Chem Rev 1999; 99: 2797-816.
Search in Google Scholar Back to article
8. Sato K, Tashiro Y, Chibana S, et al. Role of lipid-derived free radical in bleomycin-induced lung injury in mice: availability for ESR spin trap method with organic phase extraction. Biol Pharm Bull 2008; 31: 1855-9.
Search in Google Scholar Back to article
9. Chaudhary NI, Schnapp A, Park JE. Pharmacologic differentiation of inflammation and fibrosis in the rat bleomycin model. Am J Respir Crit Care Med 2006; 173: 769-76.
Search in Google Scholar Back to article
10. Sebti SM, Mignano JE, Jani JP, et al. Bleomycin hydrolase: molecular cloning, sequencing, and biochemical studies reveal membership in the cysteine proteinase family. Biochemistry 1989; 28: 6544-8.
Search in Google Scholar Back to article
11. Tomášková V Jr, Rozborilová E, Flochová E, Staško J, Kubisz P. Effect of cytostatic drugs on the endothelium and platelets. Acta Med Mart 2002; 2: 20-3.
Search in Google Scholar Back to article
12. Fleischman RW, Baker JR, Thompson GR, et al. Bleomycin-induced interstitial pneumonia in dogs. Thorax 1971; 26: 675-82.
Search in Google Scholar Back to article
13. Adamson IY, Bowden DH. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol 1974; 77: 185-97.
Search in Google Scholar Back to article
14. Thrall RS, Mccormick JR, Jack RM, et al. Bleomycin-induced pulmonary fibrosis in the rat: inhibition by indomethacin. Am J Pathol 1979; 95: 117-30.
Search in Google Scholar Back to article
15. Bale S, Sunkoju M, Reddy SS, et al. Oropharyngeal aspiration of bleomycin: An alternative experimental model of pulmonary fibrosis developed in Swiss mice. Indian J Pharmacol 2016; 48: 643–8.
Search in Google Scholar Back to article
16. Egger C, Cannet C, Gérard C, et al. Administration of Bleomycin via the Oropharyngeal Aspiration Route Leads to Sustained Lung Fibrosis in Mice and Rats as Quantified by UTE-MRI and Histology. PLoS One 2013; 8: e63432.
Search in Google Scholar Back to article
17. Zhao J, Shi W, Wang YL, et al. Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice. Am J Physiol Lung Cell Mol Physiol 2002; 282: 585-93.
Search in Google Scholar Back to article
18. Wollin L, Wex E, Pautsch A, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J 2015; 45: 1434-45.
Search in Google Scholar Back to article
19. Wollin L, Maillet I, Quesniaux V, et al. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther 2014; 349: 209-20.
Search in Google Scholar Back to article
20. Oku H, Shimizu T, Kawabata T, et al. Antifibrotic action of pirfenidone and prednisolone: different effects on pulmonary cytokines and growth factors in bleomycin-induced murine pulmonary fibrosis. Eur J Pharmacol 2008; 590: 400-8.
Search in Google Scholar Back to article
21. Maher TM. Pirfenidone in idiopathic pulmonary fibrosis. Drugs Today (Barc) 2010; 46: 473-82.
Search in Google Scholar Back to article
22. Liu W, Wan J, Han JZ, et al. Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice. Respir Res 2013; 14: 101.
Search in Google Scholar Back to article
23. Li YJ, Azuma A, Usuki J, et al. EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-beta signaling in lung fibroblasts. Respir Res 2006; 7: 16.
Search in Google Scholar Back to article
24. Ji Y, Dou YN, Zhao QW, et al. Paeoniflorin suppresses TGF- mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway. Acta Pharmacol Sin 2016; 37: 794-804.
Search in Google Scholar Back to article
25. Tang H, He H, Ji H, et al. Tanshinone IIA ameliorates bleomycin-induced pulmonary fibrosis and inhibits transforming growth factor-beta-dependent epithelial to mesenchymal transition. J Surg Res 2015; 197: 167-75.
Search in Google Scholar Back to article
26. Degryse AL, Tanjore H, Xu XC, et al. Repetitive intratracheal bleomycin models several features of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2010; 299: 442-52.
Search in Google Scholar Back to article
27. Izbicki G, Segel MJ, Christensen TG, et al. Time course of bleomycin-induced lung fibrosis. Int J Exp Pathol 2002; 83: 111-9.
Search in Google Scholar Back to article
28. Peng R, Sridhar S, Tyagi G, et al. Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for “active” disease. PLoS One 2013; 8: e59348.
Search in Google Scholar Back to article
29. Chua F, Gauldie J, Laurent GJ. Pulmonary fibrosis: searching for model answers. Am J Respir Cell Mol Biol 2005; 33: 9–13.
Search in Google Scholar Back to article
30. Moore BB, Murray L, Das A, et al. The role of CCL12 in the recruitment of fibrocytes and lung fibrosis. Am J Respir Cell Mol Biol 2006; 35: 175–81.
Search in Google Scholar Back to article
31. Roberts SN, Howie SE, Wallace WA, et al. A novel model for human interstitial lung disease: hapten-driven lung fibrosis in rodents. J Pathol 1995; 176: 309-18.
Search in Google Scholar Back to article
32. Christensen PJ, Goodman RE, Pastoriza L, et al. Induction of lung fibrosis in the mouse by intratracheal instillation of fluorescein isothiocyanate is not T-cell-dependent. Am J Pathol 1999; 155: 1773-9.
Search in Google Scholar Back to article
33. Degryse AL, Lawson WE. Progress toward improving animal models for idiopathic pulmonary fibrosis. Am J Med Sci 2011; 341: 444-9.
Search in Google Scholar Back to article
34. Karvonen RL, Fernandez-Madrid F, Maughan RL, et al. An animal model of pulmonary radiation fibrosis with biochemical, physiologic, immunologic, and morphologic observations. Radiat Res 1987; 111: 68-80.
Search in Google Scholar Back to article
35. Haston CK, Travis EL. Murine susceptibility to radiation-induced pulmonary fibrosis is influenced by a genetic factor implicated in susceptibility to bleomycin-induced pulmonary fibrosis. Cancer Res 1997; 57: 5286-91.
Search in Google Scholar Back to article
36. Morgan GW, Breit SN. Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat Oncol Biol Phys 1995; 31: 361-9.
Search in Google Scholar Back to article
37. Paun A, Kunwar A, Haston CK. Acute adaptive immune response correlates with late radiation-induced pulmonary fibrosis in mice. Radiat Oncol 2015; 10: 45.
Search in Google Scholar Back to article
38. Lakatos HF, Burgess HA, Thatcher TH, et al. Oropharyngeal aspiration of a silica suspension produces a superior model of silicosis in the mouse when compared to intratracheal instillation. Exp Lung Res 2006; 32: 181-99.
Search in Google Scholar Back to article
39. Davis GS, Leslie KO, Hemenway DR. Silicosis in mice: effects of dose, time, and genetic strain. J Environ Pathol Toxicol Oncol 1998; 17: 81-97.
Search in Google Scholar Back to article
40. Barbarin V, Nihoul A, Misson P, et al. The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis. Respir Res 2005; 6: 112.
Search in Google Scholar Back to article
41. Barbarin V, Arras M, Misson P, et al. Characterization of the effect of interleukin-10 on silica-induced lung fibrosis in mice. Am J Respir Cell Mol Biol 2004; 31: 78–85.
Search in Google Scholar Back to article
42. Hurbánková M, Kaiglová A, Buchancová J. Cytokines – the important biomarkers of lung injury after exposure to indstrial fibrous dusts. Acta Med Mart 2001; 1: 19-24.
Search in Google Scholar Back to article
43. Roggli V, Gibbs AR, Attanoos R, et al. Pathology of asbestosis: an update of the diagnostic criteria response to a critique. Arch Pathol Lab Med 2016; 140: 950-2.
Search in Google Scholar Back to article
44. Kim SJ, Cheresh P, Jablonski RP, et al. The role of mitochondrial DNA in mediating alveolar epithe lial cell apoptosis and pulmonary fibrosis. Int J Mol Sci 2015; 16: 21486-519.
Search in Google Scholar Back to article

Experimental Models of Pulmonary Fibrosis and their Translational Potential

Abstract

Paradigm

My account