This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chua, F. Articles by Laurent, G. J. Search for Related Content PubMed PubMed Citation Articles by Chua, F. Articles by Laurent, G. J.

Pulmonary Fibrosis

Searching for Model Answers

Centre for Respiratory Research, Royal Free and University College London School of Medicine, London, United Kingdom; and Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to Felix Chua, Centre for Respiratory Research, Royal Free and University College London School of Medicine, Rayne Institute, 5 University Street, London WC1E 6JJ, UK. E-mail: fjkchua{at}yahoo.co.uk

Substantial challenges remain in our understanding of fibrotic lung diseases. Nowhere is this more true than in the elucidation and verification of the pathogenetic basis upon which they develop. Scientific progress, most recently in the field of experimental therapy, has relied closely on interpreting data derived from animal modeling. Such models are used to identify the cellular interactions and molecular pathways involved in lung tissue repair and fibrosis. Over the coming years, the significance of new discoveries will continue to be evaluated using the in vivo analysis of animal models substituting for patients with actual pulmonary fibrosis. The commonest strategy to induce experimental pulmonary fibrosis is by directly administering a profibrotic agent to either wild-type animals or those that bear a specific genetic modification. The creation of new models has been greatly enhanced by the availability of stem cell lines and methods for introducing genetic mutations into these cells. Despite an increasing choice of models, there are still good reasons to continue adapting and using one of its earliest examples, the bleomycin model, in post-genomic pulmonary fibrosis research. A brief review of the exacting requirements of such research will place the strengths of this particular model in perspective.

Key Words: pulmonary fibrosis • animal models • bleomycin

This article has been cited by other articles:

				M. Mouded, E. E. Egea, M. J. Brown, S. M. Hanlon, A. M. Houghton, L. W. Tsai, E. P. Ingenito, and S. D. Shapiro Epithelial Cell Apoptosis Causes Acute Lung Injury Masquerading as Emphysema Am. J. Respir. Cell Mol. Biol., October 1, 2009; 41(4): 407 - 414. [Abstract] [Full Text] [PDF]

				A. Mitani, T. Nagase, K. Fukuchi, H. Aburatani, R. Makita, and H. Kurihara Transcriptional Coactivator with PDZ-binding Motif Is Essential for Normal Alveolarization in Mice Am. J. Respir. Crit. Care Med., August 15, 2009; 180(4): 326 - 338. [Abstract] [Full Text] [PDF]

				M. Failla, T. Genovese, E. Mazzon, M. Fruciano, E. Fagone, E. Gili, A. Barera, C. La Rosa, E. Conte, N. Crimi, et al. 16,16-Dimethyl Prostaglandin E2 Efficacy on Prevention and Protection from Bleomycin-Induced Lung Injury and Fibrosis Am. J. Respir. Cell Mol. Biol., July 1, 2009; 41(1): 50 - 58. [Abstract] [Full Text] [PDF]

				V. Martins, S. S. Valenca, F. A. Farias-Filho, R. Molinaro, R. L. Simoes, T. P. T. Ferreira, P. M. R. e Silva, C. M. Hogaboam, S. L. Kunkel, I. M. Fierro, et al. ATLa, an Aspirin-Triggered Lipoxin A4 Synthetic Analog, Prevents the Inflammatory and Fibrotic Effects of Bleomycin-Induced Pulmonary Fibrosis J. Immunol., May 1, 2009; 182(9): 5374 - 5381. [Abstract] [Full Text] [PDF]

				S. Matalon and K. B. Adler Highlights of the April Issue Am. J. Respir. Cell Mol. Biol., April 1, 2009; 40(4): 383 - 384. [Full Text] [PDF]

				J. F. Alcorn, J. van der Velden, A. L. Brown, B. McElhinney, C. G. Irvin, and Y. M. W. Janssen-Heininger c-Jun N-Terminal Kinase 1 Is Required for the Development of Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., April 1, 2009; 40(4): 422 - 432. [Abstract] [Full Text] [PDF]

				R. H. Brown, C. G. Irvin, G. B. Allen III, S. D. Shapiro, W. J. Martin, M. R. J. Kolb, D. M. Hyde, G. F. Nieman, D. D. Cody, M. Ishii, et al. An Official ATS Conference Proceedings: Advances in Small-Animal Imaging Application to Lung Pathophysiology Proceedings of the ATS, July 15, 2008; 5(5): 591 - 600. [Full Text] [PDF]

				J. W. Voltz, J. W. Card, M. A. Carey, L. M. DeGraff, C. D. Ferguson, G. P. Flake, J. C. Bonner, K. S. Korach, and D. C. Zeldin Male Sex Hormones Exacerbate Lung Function Impairment after Bleomycin-Induced Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 45 - 52. [Abstract] [Full Text] [PDF]

				H. Yu, M. Konigshoff, A. Jayachandran, D. Handley, W. Seeger, N. Kaminski, and O. Eickelberg Transgelin is a direct target of TGF-{beta}/Smad3-dependent epithelial cell migration in lung fibrosis FASEB J, June 1, 2008; 22(6): 1778 - 1789. [Abstract] [Full Text] [PDF]

				A. Clement and E. Eber Interstitial lung diseases in infants and children Eur. Respir. J., March 1, 2008; 31(3): 658 - 666. [Abstract] [Full Text] [PDF]

				C. C. Lewis, J. Y. H. Yang, X. Huang, S. K. Banerjee, M. R. Blackburn, P. Baluk, D. M. McDonald, T. S. Blackwell, V. Nagabhushanam, W. Peters, et al. Disease-Specific Gene Expression Profiling in Multiple Models of Lung Disease Am. J. Respir. Crit. Care Med., February 15, 2008; 177(4): 376 - 387. [Abstract] [Full Text] [PDF]

				J. Gauldie and M. Kolb Animal models of pulmonary fibrosis: how far from effective reality? Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L151 - L151. [Full Text] [PDF]

				J.-F. Marquis, A. Nantel, R. LaCourse, L. Ryan, R. J. North, and P. Gros Fibrotic Response as a Distinguishing Feature of Resistance and Susceptibility to Pulmonary Infection with Mycobacterium tuberculosis in Mice Infect. Immun., January 1, 2008; 76(1): 78 - 88. [Abstract] [Full Text] [PDF]

				A. R. Hemnes, A. Zaiman, and H. C. Champion PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L24 - L33. [Abstract] [Full Text] [PDF]

				A. Serrano-Mollar, M. Nacher, G. Gay-Jordi, D. Closa, A. Xaubet, and O. Bulbena Intratracheal Transplantation of Alveolar Type II Cells Reverses Bleomycin-induced Lung Fibrosis Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1261 - 1268. [Abstract] [Full Text] [PDF]

				N. Pottier, C. Chupin, V. Defamie, B. Cardinaud, R. Sutherland, G. Rios, F. Gauthier, P. J. Wolters, Y. Berthiaume, P. Barbry, et al. Relationships between Early Inflammatory Response to Bleomycin and Sensitivity to Lung Fibrosis: A Role for Dipeptidyl-Peptidase I and Tissue Inhibitor of Metalloproteinase-3? Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1098 - 1107. [Abstract] [Full Text] [PDF]

				H. Zhang, W. E. Lawson, V. V. Polosukhin, A. Pozzi, T. S. Blackwell, Y. Litingtung, and C. Chiang Inhibitor of Differentiation 1 Promotes Endothelial Survival in a Bleomycin Model of Lung Injury in Mice Am. J. Pathol., October 1, 2007; 171(4): 1113 - 1126. [Abstract] [Full Text] [PDF]

				D. Pilling, D. Roife, M. Wang, S. D. Ronkainen, J. R. Crawford, E. L. Travis, and R. H. Gomer Reduction of Bleomycin-Induced Pulmonary Fibrosis by Serum Amyloid P J. Immunol., September 15, 2007; 179(6): 4035 - 4044. [Abstract] [Full Text] [PDF]

				G. W. Hunninghake and M. I. Schwarz State of the Art. Does Current Knowledge Explain the Pathogenesis of Idiopathic Pulmonary Fibrosis?: A Perspective Proceedings of the ATS, August 15, 2007; 4(5): 449 - 452. [Abstract] [Full Text] [PDF]

				C. P. Baran, J. M. Opalek, S. McMaken, C. A. Newland, J. M. O'Brien Jr., M. G. Hunter, B. D. Bringardner, M. M. Monick, D. R. Brigstock, P. C. Stromberg, et al. Important Roles for Macrophage Colony-stimulating Factor, CC Chemokine Ligand 2, and Mononuclear Phagocytes in the Pathogenesis of Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., July 1, 2007; 176(1): 78 - 89. [Abstract] [Full Text] [PDF]

				S. Cuzzocrea, T. Genovese, M. Failla, G. Vecchio, M. Fruciano, E. Mazzon, R. Di Paola, C. Muia, C. La Rosa, N. Crimi, et al. Protective effect of orally administered carnosine on bleomycin-induced lung injury Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1095 - L1104. [Abstract] [Full Text] [PDF]

				A. U. Wells and C. M. Hogaboam Update in Diffuse Parenchymal Lung Disease 2006 Am. J. Respir. Crit. Care Med., April 1, 2007; 175(7): 655 - 660. [Full Text] [PDF]

				E. M. Pierce, K. Carpenter, C. Jakubzick, S. L. Kunkel, K. R. Flaherty, F. J. Martinez, and C. M. Hogaboam Therapeutic Targeting of CC Ligand 21 or CC Chemokine Receptor 7 Abrogates Pulmonary Fibrosis Induced by the Adoptive Transfer of Human Pulmonary Fibroblasts to Immunodeficient Mice Am. J. Pathol., April 1, 2007; 170(4): 1152 - 1164. [Abstract] [Full Text] [PDF]

				A. V. Gonzalez, F. Le Bellego, and M. S. Ludwig Imbalance of Receptor-Regulated and Inhibitory Smads in Lung Fibroblasts from Bleomycin-Exposed Rats Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 206 - 212. [Abstract] [Full Text] [PDF]

				F. Chua, S. E. Dunsmore, P. H. Clingen, S. E. Mutsaers, S. D. Shapiro, A. W. Segal, J. Roes, and G. J. Laurent Mice Lacking Neutrophil Elastase Are Resistant to Bleomycin-Induced Pulmonary Fibrosis Am. J. Pathol., January 1, 2007; 170(1): 65 - 74. [Abstract] [Full Text] [PDF]

				I. V. Yang, L. H. Burch, M. P. Steele, J. D. Savov, J. W. Hollingsworth, E. McElvania-Tekippe, K. G. Berman, M. C. Speer, T. A. Sporn, K. K. Brown, et al. Gene Expression Profiling of Familial and Sporadic Interstitial Pneumonia Am. J. Respir. Crit. Care Med., January 1, 2007; 175(1): 45 - 54. [Abstract] [Full Text] [PDF]

				A. Churg, H. Tai, T. Coulthard, R. Wang, and J. L. Wright Cigarette Smoke Drives Small Airway Remodeling by Induction of Growth Factors in the Airway Wall Am. J. Respir. Crit. Care Med., December 15, 2006; 174(12): 1327 - 1334. [Abstract] [Full Text] [PDF]

				S. D. Shapiro Animal Models of Asthma: Pro: Allergic Avoidance of Animal (Model[s]) Is Not an Option Am. J. Respir. Crit. Care Med., December 1, 2006; 174(11): 1171 - 1173. [Full Text] [PDF]

				J. Gauldie, M. Kolb, K. Ask, G. Martin, P. Bonniaud, and D. Warburton Smad3 Signaling Involved in Pulmonary Fibrosis and Emphysema Proceedings of the ATS, November 1, 2006; 3(8): 696 - 702. [Abstract] [Full Text] [PDF]

				K Nakagome, M Dohi, K Okunishi, R Tanaka, J Miyazaki, and K Yamamoto In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by inhibiting the production and activation of TGF-{beta} in the lung Thorax, October 1, 2006; 61(10): 886 - 894. [Abstract] [Full Text] [PDF]

				S. D. Shapiro Extracellular matrix in lung disease. Proceedings of the Twenty-First Transatlantic Airway Conference. Proceedings of the ATS, July 1, 2006; 3(5): 397 - 455. [Full Text] [PDF]

				N. I. Chaudhary, A. Schnapp, and J. E. Park Pharmacologic Differentiation of Inflammation and Fibrosis in the Rat Bleomycin Model Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 769 - 776. [Abstract] [Full Text] [PDF]

				G. R. S. Budinger, G. M. Mutlu, J. Eisenbart, A. C. Fuller, A. A. Bellmeyer, C. M. Baker, M. Wilson, K. Ridge, T. A. Barrett, V. Y. Lee, et al. Proapoptotic Bid is required for pulmonary fibrosis PNAS, March 21, 2006; 103(12): 4604 - 4609. [Abstract] [Full Text] [PDF]

				K. Ask, G. E. M. Martin, M. Kolb, and J. Gauldie Targeting genes for treatment in idiopathic pulmonary fibrosis: challenges and opportunities, promises and pitfalls. Proceedings of the ATS, January 1, 2006; 3(4): 389 - 393. [Abstract] [Full Text] [PDF]