Idiopathic Pulmonary Fibrosis

Kaminski, Naftali; Belperio, John A.; Bitterman, Peter B.; Chen, Li; Chensue, Stephen W.; Choi, Augustine M.K.; Đačić, Sanja; Dauber, James H.; Bois, Roland M. du; Enghild, Jan J.; Fattman, Cheryl L.; Grutters, Jan C.; Haegens, Astrid; Hanford, Lana E.; Heintz, Nicolas; Henson, Peter M.; Hogaboam, Cory M.; Kagan, Valerian E.; Keane, Michael P.; Kunkel, Steven L.; Land, Susan; Loyd, James E.; Lukacs, Nicholas W.; MacPherson, Maximilian B.; Manning, Brian J.; Manning, Nicole; Martinelli, Marcella; Möller, David R.; Morse, Danielle; Mossman, Brooke T.; Noble, Paul W.; Nowak, Norma J.; Oury, Tim D.; Pardo, Annie; Perez, A. Zambrano; Petty, Thomas L.; Phan, Sem H.; Ramos-Niño, Maria E.; Ray, Prabir; Rogers, Robert M.; Sato, Hajime; Scapoli, Luca; Schaefer, Lisa M.; Selman, Moisés; Stern, Maria; Strollo, Diane C.; Tyurin, Vladimir A.; Valnickova, Zuzana; Welsh, Kenneth I.; Witzmann, Frank A.; Yousem, Samuel A.; Strieter, Robert M.

doi:10.1165/rcmb.2003-0159su

Cited by 44 publications

(24 citation statements)

References 537 publications

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“…Expression profiling studies of the bleomycin mouse model of fibrosis (27) and five patients with IPF (28) revealed differential expression of several gene families expressed in the fibrotic lung specimens. Most of the genes upregulated in lung fibrosis encode proteins involved in extracellular matrix formation, degradation, and signaling.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Gene Expression Profiling of Familial and Sporadic Interstitial Pneumonia

Yang

Burch

Steele

et al. 2007

Am J Respir Crit Care Med

156

125

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Rationale: Idiopathic interstitial pneumonia (IIP) and its familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these subtypes are unknown. Objectives: To evaluate gene expression in the lung tissue of patients with usual interstitial pneumonia or nonspecific interstitial pneumonia that was either familial or nonfamilial in origin, and to compare it with gene expression in normal lung parenchyma. Methods: We profiled RNA from the lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9 normal control subjects on a whole human genome oligonucleotide microarray. Results: Significant transcriptional differences exist in familial and sporadic IIPs. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish IIP from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. The role of the chemokine CXCL12 in disease pathogenesis was confirmed in the murine bleomycin model of lung injury, with C57BL/6 CXCR4؉/؊ mice demonstrating significantly less collagen deposition than C57BL/6 CXCR4؉/؉ mice. Whereas substantial differences exist between familial and sporadic IIPs, we identified only minor gene expression changes between usual interstitial pneumonia and nonspecific interstitial pneumonia. Conclusions: Taken together, our findings indicate that differences in gene expression profiles between familial and sporadic IIPs may provide clues to the etiology and pathogenesis of IIP.

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Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Gene Expression Profiling of Familial and Sporadic Interstitial Pneumonia

Yang

Burch

Steele

et al. 2007

Am J Respir Crit Care Med

156

125

View full text Add to dashboard Cite

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“…3 Pulmonary fibrosis is a progressive, inflammatory condition involving enhanced deposition of extracellular matrix within the lung parenchyma. 4 The precise pathophysiology is not completely understood, but this type of fibrosis is typically seen in the setting of chronic inflammation resulting from exposure to exogenous agents.…”

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confidence: 99%

“…4 The histopathologic finding of subepithelial fibrosis observed in these conditions has been linked to airway remodeling. It is a disorder resistant to most currently available treatments and intervention has thus far focused on prevention.…”

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confidence: 99%

Erythropoietin ameliorates chemotherapy‐induced fibrosis of the lungs in a preclinical murine model

Sigounas

Salleng

Mehlhop

et al. 2008

Intl Journal of Cancer

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Organ toxicity induced by chemotherapeutic drugs is a serious obstacle in the effective treatment of patients suffering from cancer and autoimmune disease. A strong association exists between pulmonary toxicity, particularly fibrosis, and chemotherapeutic drugs. Attempts have been made to identify compounds capable of suppressing fibrosis. In addition to its erythropoietic activity, erythropoietin (EPO) has been shown to have effects on nonhemopoietic cells. Therefore, we postulated that EPO may exert beneficial effects on lung tissue during chemotherapy. To test our hypothesis, we investigated pulmonary changes caused by bleomycin, a fibrosis‐inducing agent, in animals treated with the drug alone and in combination with EPO. Fibrosis, cellular alterations and structural changes were assayed by blind analysis of the lung sections. A 6‐fold decrease in the number of prominent endothelial cells—suspected to be indicative of cellular activation and inflammatory response—was observed in lung sections derived from mice treated with bleomycin and EPO compared to animals injected with bleomycin alone (p < 0.008). Additionally, there was twice the number of ICAM1‐positive endothelial cells in animals treated with bleomycin alone compared with the number in the bleomycin and EPO‐treated group (p < 0.05). Alveolar mononuclear phagocytic hyperplasia was reduced by as much as 100% in animals treated with bleomycin and EPO compared to animals treated with bleomycin alone (p < 0.03). Finally, a 5‐fold decrease in interstitial fibrosis was observed in lung sections obtained from animals treated with bleomycin and EPO (p < 0.02). We conclude that EPO can ameliorate drug‐induced fibrosis and endothelial damage caused by chemotherapeutic agents. © 2008 Wiley‐Liss, Inc.

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“…We have recently reviewed most of the work that implemented microarrays in lung fibrosis (12,16); these included studies of animal models of fibrosis, analysis of human lungs, and analysis of cells obtained from lungs of patients with the disease. These articles and analytic approaches are summarized in Table 1.…”

Section: Microarray Analysis Of Pulmonary Fibrosismentioning

confidence: 99%

“…We have previously described the earliest articles that applied microarrays in bleomycin-induced fibrosis, including the work of Liu and colleagues, which analyzed lung gene expression profiles after bleomycin exposure in the rat and identified FIZZ1 as a potential regulator of fibrosis (12,16,17). Interestingly, much of the work using arrays in mouse lung fibrosis focused on comparing gene expression patterns in mice susceptible and resistant to fibrosis.…”

Section: Microarray Analysis Of Animal Models Of Diseasementioning

confidence: 99%

Towards Systems Biology of Human Pulmonary Fibrosis

Studer

Kaminski²

2007

Proceedings of the American Thoracic Society

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The integrated effect of multiple pathways, molecules, genetic polymorphisms, environmental stimuli, and possible infection determines the lung phenotype in idiopathic pulmonary fibrosis (IPF), a chronic progressive and often lethal lung disease. Systems biology approaches aim to provide a systemwide view of biological process using computational tools and high-throughput technologies. Although much of the analysis of genome-level transcriptional highresolution profiles of IPF was reductionist, usually focusing on a single factor in the disease process, there are some studies that implement systems approaches. We discuss these analyses and provide examples of the global analysis of IPF, hypersensitivity pneumonitis, and nonspecific interstitial pneumonia. Detailed quantitative phenotyping and correlation with microarray results as well as highthroughput genotyping should provide us with the datasets to implement systems biology approaches in fibrosis research. Interdisciplinary teams and training of junior investigators in the vocabulary of systems biology should allow us to use these datasets integratively and generate a global model of human pulmonary fibrosis.

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Idiopathic Pulmonary Fibrosis

Cited by 44 publications

References 537 publications

Gene Expression Profiling of Familial and Sporadic Interstitial Pneumonia

Gene Expression Profiling of Familial and Sporadic Interstitial Pneumonia

Erythropoietin ameliorates chemotherapy‐induced fibrosis of the lungs in a preclinical murine model

Towards Systems Biology of Human Pulmonary Fibrosis

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