https://doi.org/10.4081/reumatismo.2024.1642
Skin and lung fibrosis induced by bleomycin in mice: a systematic review
Submitted: 3 September 2023
Accepted: 2 December 2023
Published: 22 March 2024
Accepted: 2 December 2023
Abstract Views: 1453
PDF: 598
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Objective. Scleroderma, or systemic sclerosis (SSc), is a chronic autoimmune connective disease with an unknown etiology and poorly understood pathogenesis. The striking array of autoimmune, vascular, and fibrotic changes that develop in almost all patients makes SSc unique among connective tissue diseases. Although no animal model developed for SSc to date fully represents all features of human disease, some animal models that demonstrate features of SSc may help to better understand the pathogenesis of the disease and to develop new therapeutic options. In this review, we aimed to evaluate skin fibrosis and lung involvement in a bleomycin (BLM)-induced mouse model and to evaluate the differences between studies.
Methods. A systematic literature review (PRISMA guideline) on PubMed and EMBASE (until May 2023, without limits) was performed. A primary literature search was conducted using the PubMed and EMBASE databases for all articles published from 1990 to May 2023. Review articles, human studies, and non-dermatological studies were excluded. Of the 38 non-duplicated studies, 20 articles were included.
Results. Among inducible animal models, the BLM-induced SSc is still the most widely used. In recent years, the measurement of tissue thickness between the epidermal-dermal junction and the dermal-adipose tissue junction (dermal layer) has become more widely accepted.
Conclusions. In animal studies, it is important to simultaneously evaluate lung tissues in addition to skin fibrosis induced in mice by subcutaneous BLM application, following the 3R (replacement, reduction, and refinement) principle to avoid cruelty to animals.
Jimenez SA, Piera-Velazquez S. Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?. Matrix Biol 2016; 51: 26-36.
DOI: https://doi.org/10.1016/j.matbio.2016.01.012
Sierra-Sepúlveda A, Esquinca-González A, Benavides-Suárez SA, Sordo-Lima DE, Caballero-Islas AE, Cabral-Castañeda AR, et al. Systemic sclerosis pathogenesis and emerging therapies, beyond the fibroblast. Biomed Res Int 2019; 2019: 4569826.
DOI: https://doi.org/10.1155/2019/4569826
Morris E, Chrobak I, Bujor A, Hant F, Mummery C, ten Dijke P, et al. Endoglin promotes TGF-β/Smad1 signaling in scleroderma fibroblasts. J Cell Physiol 2011; 226: 3340-8.
DOI: https://doi.org/10.1002/jcp.22690
Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O’Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov 2017; 16: 843-62. Erratum: Nat Rev Drug Discov 2018; 17: 78.
DOI: https://doi.org/10.1038/nrd.2017.201
Johnson DE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol 2018; 15: 234-48.
DOI: https://doi.org/10.1038/nrclinonc.2018.8
Chakraborty D, Šumová B, Mallano T, Chen CW, Distler A, Bergmann C, et al. Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis. Nat Commun 2017; 8: 1130.
DOI: https://doi.org/10.1038/s41467-017-01236-6
Pedroza M, Le TT, Lewis K, Karmouty-Quintana H, To S, George AT, et al. STAT-3 contributes to pulmonary fibrosis through epithelial injury and fibroblast-myofibroblast differentiation. FASEB J 2016; 30: 129-40.
DOI: https://doi.org/10.1096/fj.15-273953
Dees C, Tomcik M, Palumbo-Zerr K, Distler A, Beyer C, Lang V, et al. JAK-2 as a novel mediator of the profibrotic effects of transforming growth factor β in systemic sclerosis. Arthritis Rheum 2012; 64: 3006-15.
DOI: https://doi.org/10.1002/art.34500
Wang W, Bhattacharyya S, Marangoni RG, Carns M, Dennis-Aren K, Yeldandi A, et al. The JAK/STAT pathway is activated in systemic sclerosis and is effectively targeted by tofacitinib. J Scleroderma Relat Disord 2020; 5: 40-50.
DOI: https://doi.org/10.1177/2397198319865367
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev 2021; 372: n71.
DOI: https://doi.org/10.1136/bmj.n71
Adamson IY. Drug-induced pulmonary fibrosis. Environ Health Perspect 1984; 55: 25-36.
DOI: https://doi.org/10.1289/ehp.845525
Mountz JD, Minor MBD, Turner R, Thomas MB, Richards F, Pisko E. Bleomycin-induced cutaneous toxicity in the rat: analysis of histopathology and ultrastructure compared with progressive systemic sclerosis (scleroderma). Br J Dermatol 1983; 108: 679-86.
DOI: https://doi.org/10.1111/j.1365-2133.1983.tb01080.x
Yamamoto T, Takagawa S, Katayama I, Yamazaki K, Hamazaki Y, Shinkai H, et al. Animal model of sclerotic skin. I: local injections of bleomycin induce sclerotic skin mimicking scleroderma. J Invest Dermatol 1999; 112: 456-62.
DOI: https://doi.org/10.1046/j.1523-1747.1999.00528.x
Takagawa S, Lakos G, Mori Y, Varga J, Yamamoto T, Nishioka K. Sustained activation of fibroblast transforming growth factor-β/smad signaling in a murine model of scleroderma. J Invest Dermatol 2003; 121: 41-50.
DOI: https://doi.org/10.1046/j.1523-1747.2003.12308.x
Yamamoto T, Takahashi Y, Takagawa S, Katayama I, Nishioka K. Animal model of sclerotic skin. II. Bleomycin induced scleroderma in genetically mast cell deficient WBB6F1-W/W(V) mice. J Rheumatol 1999; 26: 2628-34.
Adamson IY, Bowden DH. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol 1974; 77: 185-97.
Laurent GJ, McAnulty RJ, Corrin B, Cockerill P. Biochemical and histological changes in pulmonary fibrosis induced in rabbits with intratracheal bleomycin. Eur J Clin Invest 1981; 11: 441-8.
DOI: https://doi.org/10.1111/j.1365-2362.1981.tb02011.x
Szapiel S V, Elson NA, Fulmer JD, Hunninghake GW, Crystal RG. Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis 1979; 120: 893-9.
Clark JG, Starcher BC, Uitto J. Bleomycin-induced synthesis of type I procollagen by human lung and skin fibroblasts in culture. Biochim Biophys Acta 1980; 631: 359-70.
DOI: https://doi.org/10.1016/0304-4165(80)90309-8
Sasaki H, Sato T, Yamauchi N, Okamoto T, Kobayashi D, Iyama S, et al. Induction of heat shock protein 47 synthesis by TGF-β and IL-1β via enhancement of the heat shock element binding activity of heat shock transcription factor 1. J Immunol 2002; 168: 5178-83.
DOI: https://doi.org/10.4049/jimmunol.168.10.5178
Yamamoto T, Nishioka K. Animal model of sclerotic skin. V: increased expression of α-smooth muscle actin in fibroblastic cells in bleomycin-induced scleroderma. Clin Immunol 2002; 102: 77-83.
DOI: https://doi.org/10.1006/clim.2001.5138
Jeong JH. Inducible mouse models for cancer drug target validation. J Cancer Prev 2016; 21: 243-8.
DOI: https://doi.org/10.15430/JCP.2016.21.4.243
Paul Chowdhury B, Gorska MM. Modeling asthma in mice using common aeroallergens. Methods Mol Biol 2022; 2506:1-18.
DOI: https://doi.org/10.1007/978-1-0716-2364-0_1
Yamamoto T, Nishioka K. Animal model of sclerotic skin. VI: evaluation of bleomycin-induced skin sclerosis in nude mice. Arch Dermatol Res 2004; 295: 453-6.
DOI: https://doi.org/10.1007/s00403-003-0439-y
Lazo JS, Humphreys CJ. Lack of metabolism as the biochemical basis of bleomycin-induced pulmonary toxicity. Proc Natl Acad Sci 1983; 80: 3064-8.
DOI: https://doi.org/10.1073/pnas.80.10.3064
King TE, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet 2011; 378: 1949-61.
DOI: https://doi.org/10.1016/S0140-6736(11)60052-4
Lee R, Reese C, Bonner M, Tourkina E, Hajdu Z, Riemer EC, et al. Bleomycin delivery by osmotic minipump: similarity to human scleroderma interstitial lung disease. Am J Physiol Lung Cell Mol Physiol 2014; 306: L736-48.
DOI: https://doi.org/10.1152/ajplung.00210.2013
Marangoni RG, Datta P, Paine A, Duemmel S, Nuzzo M, Sherwood L, et al. Thy-1 plays a pathogenic role and is a potential biomarker for skin fibrosis in scleroderma. JCI Insight 2022; 7: e149426.
DOI: https://doi.org/10.1172/jci.insight.149426
Zhao C, Matsushita T, Ha Nguyen VT, Tennichi M, Fujimoto M, Takehara K, et al. CD22 and CD72 contribute to the development of scleroderma in a murine model. J Dermatol Sci 2020; 97: 66-76.
DOI: https://doi.org/10.1016/j.jdermsci.2019.12.007
Ravanetti F, Ferrini E, Ragionieri L, Khalajzeyqami Z, Nicastro M, Ridwan Y, et al. SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib. Sci Rep 2021; 11: 18513.
DOI: https://doi.org/10.1038/s41598-021-97728-z
Liang M, Lv J, Zou L, Yang W, Xiong Y, Chen X, et al. A modified murine model of systemic sclerosis: Bleomycin given by pump infusion induced skin and pulmonary inflammation and fibrosis. Lab Invest 2015; 95: 342-50.
DOI: https://doi.org/10.1038/labinvest.2014.145
Ishikawa H, Takeda K, Okamoto A, Matsuo SI, Isobe KI. Induction of autoimmunity in a bleomycin-induced murine model of experimental systemic sclerosis: an important role for CD4+ T cells. J Invest Dermatol 2009; 129: 1688-95.
DOI: https://doi.org/10.1038/jid.2008.431
Yamamoto T, Kuroda M, Nishioka K. Animal model of sclerotic skin. III: histopathological comparison of bleomycin-induced scleroderma in various mice strains. Arch Dermatol Res 2000; 292: 535-41.
DOI: https://doi.org/10.1007/s004030000183
Xu X, Chen Z, Zhu X, Wang D, Liang J, Zhao C, et al. S100A9 aggravates bleomycin-induced dermal fibrosis in mice via activation of ERK1/2 MAPK and NF-κB pathways. Iran J Basic Med Sci 2018; 21: 194-201.
Rosa I, Romano E, Fioretto BS, Guasti D, Ibba-Manneschi L, Matucci-Cerinic M, et al. Scleroderma-like impairment in the network of telocytes/CD34+ stromal cells in the experimental mouse model of bleomycin-induced dermal fibrosis. Int J Mol Sci 2021; 22: 12407.
DOI: https://doi.org/10.3390/ijms222212407
Jun JB, Kim JK, Na YI, Jang SM, Paik SS, Kim YH. A convenient method for producing the bleomycin-induced mouse model of scleroderma by weekly injections using a methylcellulose gel. Rheumatol Int 2012; 32: 1443-7.
DOI: https://doi.org/10.1007/s00296-011-1884-0
Kanno Y, Kuroki A, Okada K, Tomogane K, Ueshima S, Matsuo O, et al. α2-antiplasmin is involved in the production of transforming growth factor β1 and fibrosis. J Thromb Haemost 2007; 5: 2266-73.
DOI: https://doi.org/10.1111/j.1538-7836.2007.02745.x
Yamamoto T. Intradermal injections of bleomycin to model skin fibrosis. In: Rittié L (ed.). New York, NY: Springer New York; 2017. pp 43-7.
DOI: https://doi.org/10.1007/978-1-4939-7113-8_3
Ruzehaji N, Avouac J, Elhai M, Frechet M, Frantz C, Ruiz B, et al. Combined effect of genetic background and gender in a mouse model of bleomycin-induced skin fibrosis. Arthritis Res Ther 2015; 17: 145.
DOI: https://doi.org/10.1186/s13075-015-0659-5
Oi M, Yamamoto T, Nishioka K. Increased expression of TGF-β1 in the sclerotic skin in bleomycin- “susceptible” mouse strains. J Med Dent Sci 2004; 51: 7-17.
Shibusawa Y, Negishi I, Tabata Y, Ishikawa O. Mouse model of dermal fibrosis induced by one-time injection of bleomycin-poly(L-lactic acid) microspheres. Rheumatology (Oxford) 2008; 47: 454-7.
DOI: https://doi.org/10.1093/rheumatology/ken058
Yamamoto T, Nishioka K. Possible Role of Apoptosis in the Pathogenesis of Bleomycin-Induced Scleroderma. J Invest Dermatol 2004; 122: 44-50.
DOI: https://doi.org/10.1046/j.0022-202X.2003.22121.x
Błyszczuk P, Kozlova A, Guo Z, Kania G, Distler O. Experimental mouse model of bleomycin-induced skin fibrosis. Curr Protoc Immunol 2019; 126: e88.
DOI: https://doi.org/10.1002/cpim.88
Russell WMS, Burch RL. The principles of humane experimental technique. Wheathampstead, Hertfordshire, UK: Universities Federation For Animal Welfare1960.
Wells DJ. Animal welfare and the 3Rs in European biomedical research. Ann N Y Acad Sci 2011; 1245: 14-6.
DOI: https://doi.org/10.1111/j.1749-6632.2011.06335.x
Akesson A. Longitudinal development of skin involvement and reliability of high frequency ultrasound in systemic sclerosis. Ann Rheum Dis 2004; 63: 791-6.
DOI: https://doi.org/10.1136/ard.2003.012146
El-Zawahry MBM, Abdel El-Hameed El-Cheweikh HM, Abd-El-Rahman Ramadan S, Ahmed Bassiouny D, Mohamed Fawzy M. Ultrasound biomicroscopy in the diagnosis of skin diseases. Eur J Dermatol 2007; 17: 469-75.
Hesselstrand R, Scheja A, Wildt M, Akesson A. High-frequency ultrasound of skin involvement in systemic sclerosis reflects oedema, extension and severity in early disease. Rheumatology (Oxford) 2008; 47: 84-7.
DOI: https://doi.org/10.1093/rheumatology/kem307
Jasaitiene D, Valiukeviciene S, Linkeviciute G, Raisutis R, Jasiuniene E, Kazys R. Principles of high-frequency ultrasonography for investigation of skin pathology. J Eur Acad Dermatol Venereol 2011; 25: 375-82.
DOI: https://doi.org/10.1111/j.1468-3083.2010.03837.x
Kaloudi O, Bandinelli F, Filippucci E, Conforti ML, Miniati I, Guiducci S, et al. High frequency ultrasound measurement of digital dermal thickness in systemic sclerosis. Ann Rheum Dis 2010; 69: 1140-3.
DOI: https://doi.org/10.1136/ard.2009.114843
Kleinerman R, Whang TB, Bard RL, Marmur ES. Ultrasound in dermatology: principles and applications. J Am Acad Dermatol 2012; 67: 478-87.
DOI: https://doi.org/10.1016/j.jaad.2011.12.016
Steen VD, Medsger TA. Improvement in skin thickening in systemic sclerosis associated with improved survival. Arthritis Rheum 2001; 44: 2828-35.
DOI: https://doi.org/10.1002/1529-0131(200112)44:12<2828::AID-ART470>3.0.CO;2-U
Clements PJ, Lachenbruch PA, Ng SC, Simmons M, Sterz M, Furst DE. Skin score: a semiquantitative measure of cutaneous involvement that improves prediction of prognosis in systemic sclerosis. Arthritis Rheum 2010; 33: 1256-63.
DOI: https://doi.org/10.1002/art.1780330828
Scheja A, Akesson A. Comparison of high frequency (20 MHz) ultrasound and palpation for the assessment of skin involvement in systemic sclerosis (scleroderma). Clin Exp Rheumatol 1997; 15: 283-8.
Elhai M, Jérôme Avouac, Marchiol C, Renault G, Ruiz B, Fréchet M, et al. Performance of skin ultrasound to measure skin involvement in different animal models of systemic sclerosis. Ultrasound Med Biol 2013; 39: 845-52.
DOI: https://doi.org/10.1016/j.ultrasmedbio.2012.12.002
Moore BB, Lawson WE, Oury TD, Sisson TH, Raghavendran K, Hogaboam CM. Animal models of fibrotic lung disease. Am J Respir Cell Mol Biol 2013; 49: 167-79.
DOI: https://doi.org/10.1165/rcmb.2013-0094TR
Gammon ST, Foje N, Brewer EM, Owers E, Downs CA, Budde MD, et al. Preclinical anatomical, molecular, and functional imaging of the lung with multiple modalities. Am J Physiol Cell Mol Physiol 2014; 306: L897-914.
DOI: https://doi.org/10.1152/ajplung.00007.2014
Clark DP, Badea CT. Micro-CT of rodents: state-of-the-art and future perspectives. Phys Med 2014; 30: 619-34.
DOI: https://doi.org/10.1016/j.ejmp.2014.05.011
Bidola P, Martins de Souza e Silva J, Achterhold K, Munkhbaatar E, Jost PJ, Meinhardt AL, et al. A step towards valid detection and quantification of lung cancer volume in experimental mice with contrast agent-based X-ray microtomography. Sci Rep 2019; 9: 1325.
DOI: https://doi.org/10.1038/s41598-018-37394-w
Saito S, Murase K. Detection and early phase assessment of radiation-induced lung injury in mice using micro-CT. PLoS One 2012; 7: e45960.
DOI: https://doi.org/10.1371/journal.pone.0045960
Ninaber MK, Stolk J, Smit J, Le Roy EJ, Kroft LJM, Els Bakker M, et al. Lung structure and function relation in systemic sclerosis: application of lung densitometry. Eur J Radiol 2015; 84: 975-9.
DOI: https://doi.org/10.1016/j.ejrad.2015.01.012
Perez JR, Lee S, Ybarra N, Maria O, Serban M, Jeyaseelan K, et al. A comparative analysis of longitudinal computed tomography and histopathology for evaluating the potential of mesenchymal stem cells in mitigating radiation-induced pulmonary fibrosis. Sci Rep 2017; 7: 9056.
DOI: https://doi.org/10.1038/s41598-017-09021-7
Colombi D, Dinkel J, Weinheimer O, Obermayer B, Buzan T, Nabers D, et al. Visual vs fully automatic histogram-based assessment of idiopathic pulmonary fibrosis (IPF) progression using sequential multidetector computed tomography (MDCT). PLoS One 2015; 10: e0130653.
DOI: https://doi.org/10.1371/journal.pone.0130653
Mah K, Van Dyk J. Quantitative measurement of changes in human lung density following irradiation. Radiother Oncol 1988; 11: 169-79.
DOI: https://doi.org/10.1016/0167-8140(88)90253-8
Beyer C, Schett G, Distler O, Distler JHW. Animal models of systemic sclerosis: prospects and limitations. Arthritis Rheum 2010; 62: 2831-44.
DOI: https://doi.org/10.1002/art.27647
Yamamoto T. Animal model of systemic sclerosis. J Dermatol 2010; 37: 26-41.
DOI: https://doi.org/10.1111/j.1346-8138.2009.00764.x
Kissin EY, Schiller AM, Gelbard RB, Anderson JJ, Falanga V, Simms RW, et al. Durometry for the assessment of skin disease in systemic sclerosis. Arthritis Rheum 2006; 55: 603-9.
DOI: https://doi.org/10.1002/art.22093
Salmhofer W, Rieger E, Soyer HP, Smolle J, Kerl H. Influence of skin tension and formalin fixation on sonographic measurement of tumor thickness. J Am Acad Dermatol 1996; 34: 34-9.
DOI: https://doi.org/10.1016/S0190-9622(96)90831-2
Tedstone JL, Richards SM, Garman RD, Ruzek MC. Ultrasound imaging accurately detects skin thickening in a mouse scleroderma model. Ultrasound Med Biol 2008; 34: 1239-47.
DOI: https://doi.org/10.1016/j.ultrasmedbio.2008.01.013
McDonald B, Spicer J, Giannais B, Fallavollita L, Brodt P, Ferri LE. Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms. Int J Cancer 2009; 125: 1298-305.
DOI: https://doi.org/10.1002/ijc.24409
Haupt W, Riese J, Mehler C, Weber K, Zowe M, Hohenberger W. Monocyte function before and after surgical trauma. Dig Surg 1998; 15: 102-4.
DOI: https://doi.org/10.1159/000018601
Flecknell P. Replacement, reduction and refinement. ALTEX 2002; 19: 73-8.
Tannenbaum J, Bennett BT. Russell and Burch’s 3Rs then and now: the need for clarity in definition and purpose. J Am Assoc Lab Anim Sci 2015; 54: 120-32.
How to Cite
Gülle, S., Çelik, A., Birlik, M., & Yılmaz, O. (2024). Skin and lung fibrosis induced by bleomycin in mice: a systematic review. Reumatismo, 76(1). https://doi.org/10.4081/reumatismo.2024.1642
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