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
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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.
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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.
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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.
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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
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Journal ArticleDOI
Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis.
Thomas H. Sisson,Michael Mendez,Karen Choi,Natalya Subbotina,Anthony J. Courey,Andrew K. Cunningham,Aditi Dave,John F. Engelhardt,Xiaoming Liu,Eric S. White,Victor J. Thannickal,Bethany B. Moore,Paul J. Christensen,Richard Simon +13 more
TL;DR: The development of lung fibrosis in the setting of type II cell injury in this model provides evidence for a causal link between the epithelial defects seen in idiopathic pulmonary fibrosis and the corresponding areas of scarring.
Journal ArticleDOI
Clinical and pathologic features of familial interstitial pneumonia.
Mark P. Steele,Marcy C. Speer,James E. Loyd,Kevin K. Brown,Aretha Herron,Susan H. Slifer,Lauranell H. Burch,Momen M. Wahidi,John A. Phillips,Thomas A. Sporn,H. Page McAdams,Marvin I. Schwarz,David A. Schwartz +12 more
TL;DR: It is suggested that FIP may be caused by an interaction between a specific environmental exposure and a gene (or genes) that predisposes to the development of several subtypes of idiopathic interstitial pneumonia.
Journal ArticleDOI
Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function.
TL;DR: This review summarizes recent molecular, biochemical and cell biological analyses together with clinical studies that have led to the correlation of molecular pathology with clinical manifestations and led to insights into such diverse disease processes such as albinism, fibrosis, hemorrhage, and congenital neutropenia.
Journal ArticleDOI
Early Growth Response Gene 1–mediated Apoptosis Is Essential for Transforming Growth Factor β1–induced Pulmonary Fibrosis
Chun Geun Lee,Soo Jung Cho,Min-Jong Kang,Svetlana P. Chapoval,Patty J. Lee,Paul W. Noble,Teshome Yehualaeshet,Binfeng Lu,Richard A. Flavell,Jeffrey Milbrandt,Robert J. Homer,Jack A. Elias +11 more
TL;DR: It is demonstrated that Egr-1–mediated apoptosis is a prerequisite for TGF-β1–induced fibrosis and remodeling and defined the critical role of Egr–1 in the TGF–β1 phenotype.
Journal ArticleDOI
Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling
Bethany B. Moore,Robert Paine,Paul J. Christensen,Thomas A. Moore,Stephanie Sitterding,Rose Ngan,Carol A. Wilke,William A. Kuziel,Galen B. Toews +8 more
TL;DR: It is demonstrated that CCR2−/− mice are protected from fibrosis in both the FITC and bleomycin pulmonary fibrosis models, and the protection is not explained by differences in acute lung injury, or the magnitude or composition of inflammatory cells.
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