Animal models of fibrotic lung disease.
Bethany B. Moore,William Lawson,William Lawson,Tim D. Oury,Thomas H. Sisson,Krishnan Raghavendran,Cory M. Hogaboam +6 more
TLDR
Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease and has a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis.Abstract:
Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell–cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease.read more
Citations
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Journal ArticleDOI
Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis
Arun C. Habermann,Austin J. Gutierrez,Linh T. Bui,Stephanie L. Yahn,Nichelle I. Winters,Carla L. Calvi,Lance M. Peter,Mei-I Chung,Chase J. Taylor,Christopher S. Jetter,Latha Raju,Jamie Roberson,Guixiao Ding,Lori Wood,Jennifer M.S. Sucre,Bradley W. Richmond,Bradley W. Richmond,Ana P. Serezani,Wyatt J. McDonnell,Simon B. Mallal,Simon B. Mallal,Matthew J. Bacchetta,James E. Loyd,Ciara M. Shaver,Lorraine B. Ware,Ross M. Bremner,Rajat Walia,Timothy S. Blackwell,Timothy S. Blackwell,Timothy S. Blackwell,Nicholas E. Banovich,Jonathan A. Kropski,Jonathan A. Kropski,Jonathan A. Kropski +33 more
TL;DR: It is reported that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and several previously unrecognized epithelialcell phenotypes are identified, including a KRT5−/KRT17+ pathologic, ECM-producing epithel cell population that was highly enriched in PF lungs.
Journal ArticleDOI
The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease.
Gerald Burgstaller,Bettina Oehrle,Michael Gerckens,Eric S. White,Herbert B. Schiller,Oliver Eickelberg +5 more
TL;DR: This review summarises the available data about the structure and function of the pulmonary ECM, and highlights changes that occur in idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma and lung cancer.
Journal ArticleDOI
Evasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases.
Boris Hinz,David Lagares +1 more
TL;DR: Targeting myofibroblast apoptosis and reprogramming these cells to become scar-resolving cells are emerging as novel therapeutic strategies to reverse established fibrosis.
Journal ArticleDOI
An Official American Thoracic Society Workshop Report: Use of Animal Models for the Preclinical Assessment of Potential Therapies for Pulmonary Fibrosis.
R. Gisli Jenkins,Bethany B. Moore,Rachel C. Chambers,Oliver Eickelberg,Melanie Königshoff,Martin Kolb,Geoffrey J. Laurent,Carmel B. Nanthakumar,Mitchell Alan Olman,Annie Pardo,Moises Selman,Dean Sheppard,Patricia J. Sime,Andrew M. Tager,Amanda L. Tatler,Victor J. Thannickal,Eric S. White +16 more
TL;DR: The consensus view is that use of the murine intratracheal bleomycin model in animals of both genders, using hydroxyproline measurements for collagen accumulation along with histologic assessments, is the best‐characterized animal model available for preclinical testing.
Journal ArticleDOI
Resolution of organ fibrosis
Joon Il Jun,Lester F. Lau +1 more
TL;DR: The present knowledge and gaps in the understanding of how matrix degradation is regulated and how myofibroblast cell fates can be manipulated are discussed, areas that may identify potential therapeutic approaches for fibrosis.
References
More filters
Journal ArticleDOI
Involvement of Epstein-Barr virus latent membrane protein 1 in disease progression in patients with idiopathic pulmonary fibrosis
Katsunori Tsukamoto,Hiroshi Hayakawa,Atsuhiko Sato,Kingo Chida,Hirotoshi Nakamura,Katsutoshi Miura +5 more
TL;DR: EBV LMP1 positivity may be associated with more rapid disease progression in IPF, and the role of Epstein-Barr virus in idiopathic pulmonary fibrosis is uncertain.
Journal ArticleDOI
The Alveolar Epithelium Determines Susceptibility to Lung Fibrosis in Hermansky-Pudlak Syndrome
Lisa R. Young,Peter M. Gulleman,James P. Bridges,Timothy E. Weaver,Gail H. Deutsch,Timothy S. Blackwell,Francis X. McCormack +6 more
TL;DR: It is concluded that pulmonary fibrosis in naturally occurring HPS mice is driven by intracellular trafficking defects that lower the threshold for pulmonary epithelial apoptosis and demonstrates a pivotal role for the alveolar epithelium in the maintenance ofAlveolar homeostasis and regulation of alveolars macrophage activation.
Journal ArticleDOI
Resolution of acute lung injury and inflammation – a translational mouse model
TL;DR: A translational mouse model of ALI which not only reflects the major clinical and pathological features but also enables investigation into ALI resolution is developed, indicating that this resolving model of acid aspiration represents a powerful experimental tool to investigate the injurious, inflammatory, fibrotic, and resolving and reparative processes of ALi.
Journal ArticleDOI
Pulmonary toxicity of antitumor agents
Journal ArticleDOI
Failure of mechanical properties to parallel changes in lung connective tissue composition in bleomycin-induced pulmonary fibrosis in hamsters.
TL;DR: In interstitial pulmonary fibrosis induced with bleomycin the pattern of changing biochemical composition of the lungs cannot be inferred from the lung volumes or V-P relations, and the ratios of collagen or elastin to total protein, dry lung weight, or DNA cannot be used as indicators of the amounts of these proteins in the whole lung.
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