The pathogenesis of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an appalling prognosis. The failure of anti-inflammatory therapies coupled with the observation that deranged epithelium overlies proliferative myofibroblasts to form the fibroblastic focus has lead to the emerging concept that IPF is a disease of deregulated epithelial-mesenchymal crosstalk. IPF is triggered by an as yet unidentified alveolar injury that leads to activation of transforming growth factor-β (TGF-β) and alveolar basement membrane disruption. In the presence of persisting injurious pathways, or disrupted repair pathways, activated TGF-β can lead to enhanced epithelial apoptosis and epithelial-to-mesenchymal transition (EMT) as well as fibroblast, and fibrocyte, transformation into myofibroblasts which are resistant to apoptosis. The resulting deposition of excess disrupted matrix by these myofibroblasts leads to the development of IPF.

[1]  G. Raghu,et al.  Telomere Lengths, Pulmonary Fibrosis and Telomerase (TERT) Mutations , 2010, PloS one.

[2]  S. Harari,et al.  IPF: new insight on pathogenesis and treatment , 2010, Allergy.

[3]  W. Coward,et al.  Repression of IP-10 by Interactions between Histone Deacetylation and Hypermethylation in Idiopathic Pulmonary Fibrosis , 2010, Molecular and Cellular Biology.

[4]  T. Wynn,et al.  Bleomycin and IL-1β–mediated pulmonary fibrosis is IL-17A dependent , 2010, The Journal of experimental medicine.

[5]  G. Raghu,et al.  Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology , 2010, European Respiratory Journal.

[6]  A. Sali,et al.  Comparison of human solute carriers , 2010, Protein science : a publication of the Protein Society.

[7]  R. Kairalla,et al.  Abnormal expression of telomerase/apoptosis limits type II alveolar epithelial cell replication in the early remodeling of usual interstitial pneumonia/idiopathic pulmonary fibrosis. , 2010, Human pathology.

[8]  Arnoud Sonnenberg,et al.  Integrin–TGF‐β crosstalk in fibrosis, cancer and wound healing , 2010, EMBO reports.

[9]  E. White,et al.  Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis. , 2010, American journal of respiratory and critical care medicine.

[10]  N. Kaminski,et al.  CD28 Down-Regulation on Circulating CD4 T-Cells Is Associated with Poor Prognoses of Patients with Idiopathic Pulmonary Fibrosis , 2010, PloS one.

[11]  G. Rosen,et al.  SPARC Suppresses Apoptosis of Idiopathic Pulmonary Fibrosis Fibroblasts through Constitutive Activation of β-Catenin* , 2010, The Journal of Biological Chemistry.

[12]  B. Hinz,et al.  The myofibroblast: paradigm for a mechanically active cell. , 2010, Journal of biomechanics.

[13]  Oliver Eickelberg,et al.  WNT signaling in lung disease: a failure or a regeneration signal? , 2010, American journal of respiratory cell and molecular biology.

[14]  G. Laurent,et al.  The quest for the initial lesion in idiopathic pulmonary fibrosis: gene expression differences in IPF fibroblasts. , 2010, American journal of respiratory cell and molecular biology.

[15]  A. Manicone,et al.  Cell Injury , Repair , Aging and Apoptosis Matrilysin ( Matrix Metalloproteinase-7 ) Regulates Anti-Inflammatory and Antifibrotic Pulmonary Dendritic Cells That Express CD 103 ( E 7-Integrin ) , 2010 .

[16]  Z. Werb,et al.  Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages. , 2009, Journal of Clinical Investigation.

[17]  B. Willis,et al.  N-acetylcysteine inhibits alveolar epithelial-mesenchymal transition. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[18]  R. Strieter,et al.  New mechanisms of pulmonary fibrosis. , 2009, Chest.

[19]  J. Lasky,et al.  Abrogation of TGF-beta1-induced fibroblast-myofibroblast differentiation by histone deacetylase inhibition. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[20]  M. Rojas,et al.  Twist: A Regulator of Epithelial-Mesenchymal Transition in Lung Fibrosis , 2009, PloS one.

[21]  E. Neilson,et al.  Contribution of epithelial-derived fibroblasts to bleomycin-induced lung fibrosis. , 2009, American journal of respiratory and critical care medicine.

[22]  A. Nicholson,et al.  Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. , 2009, The Journal of clinical investigation.

[23]  M. Armanios Syndromes of telomere shortening. , 2009, Annual review of genomics and human genetics.

[24]  S. Sahn,et al.  Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial , 2009, The Lancet.

[25]  J. Egan,et al.  CUX1/Wnt signaling regulates epithelial mesenchymal transition in EBV infected epithelial cells. , 2009, Experimental cell research.

[26]  V. Aidinis,et al.  Global impairment of CD4+CD25+FOXP3+ regulatory T cells in idiopathic pulmonary fibrosis. , 2009, American journal of respiratory and critical care medicine.

[27]  S. Amini,et al.  Monocyte chemoattractant protein-1 (MCP-1): an overview. , 2009, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[28]  W. Seeger,et al.  WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis. , 2009, The Journal of clinical investigation.

[29]  P. Weinreb,et al.  Lysophosphatidic acid induces alphavbeta6 integrin-mediated TGF-beta activation via the LPA2 receptor and the small G protein G alpha(q). , 2009, The American journal of pathology.

[30]  P. O'Byrne,et al.  Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. , 2009, American journal of respiratory and critical care medicine.

[31]  W. Coward,et al.  Defective Histone Acetylation Is Responsible for the Diminished Expression of Cyclooxygenase 2 in Idiopathic Pulmonary Fibrosis , 2009, Molecular and Cellular Biology.

[32]  R. Johns,et al.  Pulmonary epithelium is a prominent source of proteinase-activated receptor-1-inducible CCL2 in pulmonary fibrosis. , 2009, American journal of respiratory and critical care medicine.

[33]  N. Kaminski,et al.  WNT5A is a regulator of fibroblast proliferation and resistance to apoptosis. , 2009, American journal of respiratory cell and molecular biology.

[34]  T. Wynn,et al.  Pulmonary fibrosis: pathogenesis, etiology and regulation , 2009, Mucosal Immunology.

[35]  P. Wolters,et al.  Epithelial cell alpha3beta1 integrin links beta-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis. , 2008, The Journal of clinical investigation.

[36]  A. Knox,et al.  Novel regulation of vascular endothelial growth factor-A (VEGF-A) by transforming growth factor (beta)1: requirement for Smads, (beta)-CATENIN, AND GSK3(beta). , 2008, The Journal of biological chemistry.

[37]  S. Kudoh,et al.  A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis , 2008, Journal of Medical Genetics.

[38]  P. Lansdorp,et al.  Short telomeres are a risk factor for idiopathic pulmonary fibrosis , 2008, Proceedings of the National Academy of Sciences.

[39]  W. Seeger,et al.  Transgelin is a direct target of TGF‐β/Smad3‐dependent epithelial cell migration in lung fibrosis , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[40]  A. Knox,et al.  Tryptase activates TGFbeta in human airway smooth muscle cells via direct proteolysis. , 2008, Biochemical and biophysical research communications.

[41]  W. Seeger,et al.  Functional Wnt Signaling Is Increased in Idiopathic Pulmonary Fibrosis , 2008, PloS one.

[42]  S. Bhasin,et al.  The Effects of Myostatin on Adipogenic Differentiation of Human Bone Marrow-derived Mesenchymal Stem Cells Are Mediated through Cross-communication between Smad3 and Wnt/β-Catenin Signaling Pathways* , 2008, Journal of Biological Chemistry.

[43]  F. Nicoletti,et al.  TGF-beta1 targets the GSK-3beta/beta-catenin pathway via ERK activation in the transition of human lung fibroblasts into myofibroblasts. , 2008, Pharmacological research.

[44]  N. Kaminski,et al.  Idiopathic Pulmonary Fibrosis: Aberrant Recapitulation of Developmental Programs? , 2008, PLoS medicine.

[45]  P. Weinreb,et al.  Inhibition of Integrin αvβ6, an Activator of Latent Transforming Growth Factor-β, Prevents Radiation-induced Lung Fibrosis , 2008 .

[46]  Nicola J. Rinaldi,et al.  Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation. , 2008, American journal of respiratory and critical care medicine.

[47]  P. Weinreb,et al.  Inhibition of integrin alpha(v)beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis. , 2008, American journal of respiratory and critical care medicine.

[48]  M. Selman,et al.  Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis. , 2008, The international journal of biochemistry & cell biology.

[49]  J. Wain,et al.  The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak , 2008, Nature Medicine.

[50]  Nicola J. Rinaldi,et al.  Partial Inhibition of Integrin αvβ6 Prevents Pulmonary Fibrosis without Exacerbating Inflammation , 2008 .

[51]  B. Hinz,et al.  Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix , 2007, The Journal of cell biology.

[52]  I. Adcock,et al.  Epigenetic regulation of airway inflammation. , 2007, Current opinion in immunology.

[53]  G. Baretton,et al.  Expression of the Immunomodulator IL-10 in Type I Pneumocytes of the Rat: Alterations of IL-10 Expression in Radiation-induced Lung Damage , 2007, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[54]  Yuanyuan Xiao,et al.  Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients. , 2007, The Journal of clinical investigation.

[55]  R. Chambers,et al.  Molecular targets in pulmonary fibrosis: the myofibroblast in focus. , 2007, Chest.

[56]  C. Heldin,et al.  Signaling networks guiding epithelial–mesenchymal transitions during embryogenesis and cancer progression , 2007, Cancer science.

[57]  R. Kalluri,et al.  Fibroblasts Derive from Hepatocytes in Liver Fibrosis via Epithelial to Mesenchymal Transition* , 2007, Journal of Biological Chemistry.

[58]  M. Burdick,et al.  Differentiation of Human Circulating Fibrocytes as Mediated by Transforming Growth Factor-β and Peroxisome Proliferator-activated Receptor γ* , 2007, Journal of Biological Chemistry.

[59]  P. Shaul,et al.  Endothelin-1 induces alveolar epithelial-mesenchymal transition through endothelin type A receptor-mediated production of TGF-beta1. , 2007, American journal of respiratory cell and molecular biology.

[60]  G. Hunninghake,et al.  Important roles for macrophage colony-stimulating factor, CC chemokine ligand 2, and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis. , 2007, American journal of respiratory and critical care medicine.

[61]  Chao Xing,et al.  Adult-onset pulmonary fibrosis caused by mutations in telomerase , 2007, Proceedings of the National Academy of Sciences.

[62]  Hideki Yamamoto,et al.  Multiplicity of the interactions of Wnt proteins and their receptors. , 2007, Cellular signalling.

[63]  P. Lansdorp,et al.  Telomerase mutations in families with idiopathic pulmonary fibrosis. , 2007, The New England journal of medicine.

[64]  J. Roes,et al.  Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary fibrosis. , 2007, The American journal of pathology.

[65]  M. Burdick,et al.  Differentiation of human circulating fibrocytes as mediated by transforming growth factor-beta and peroxisome proliferator-activated receptor gamma. , 2007, The Journal of biological chemistry.

[66]  Ivana V. Yang,et al.  Gene expression profiling of familial and sporadic interstitial pneumonia. , 2007, American journal of respiratory and critical care medicine.

[67]  F Verrecchia,et al.  [Cellular and molecular mechanisms of fibrosis]. , 2006, Annales de pathologie.

[68]  Adam Byron,et al.  Integrin ligands at a glance , 2006, Journal of Cell Science.

[69]  G. Oster,et al.  Incidence and prevalence of idiopathic pulmonary fibrosis. , 2006, American journal of respiratory and critical care medicine.

[70]  K. Brown,et al.  Fibroblast foci are not discrete sites of lung injury or repair: the fibroblast reticulum. , 2006, American journal of respiratory and critical care medicine.

[71]  D. Sheppard,et al.  Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix , 2006, Proceedings of the National Academy of Sciences.

[72]  K. Nakagome,et al.  In vivo IL-10 gene delivery attenuates bleomycin induced pulmonary fibrosis by inhibiting the production and activation of TGF-β in the lung , 2006, Thorax.

[73]  R. Bloigu,et al.  Relationship between histopathological features and the course of idiopathic pulmonary fibrosis/usual interstitial pneumonia , 2006, Thorax.

[74]  R. Chambers,et al.  Ligation of protease-activated receptor 1 enhances alpha(v)beta6 integrin-dependent TGF-beta activation and promotes acute lung injury. , 2006, The Journal of clinical investigation.

[75]  J. Loyd,et al.  The genetic approach in pulmonary fibrosis: can it provide clues to this complex disease? , 2006, Proceedings of the American Thoracic Society.

[76]  D. Coultas,et al.  Is idiopathic pulmonary fibrosis an environmental disease? , 2006, Proceedings of the American Thoracic Society.

[77]  Xing Shen,et al.  Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells. , 2006, Genes & development.

[78]  M. Jinnin,et al.  Increased Expression of Integrin αvβ5 Induces the Myofibroblastic Differentiation of Dermal Fibroblasts , 2006 .

[79]  J. Thiery,et al.  Complex networks orchestrate epithelial–mesenchymal transitions , 2006, Nature Reviews Molecular Cell Biology.

[80]  Naftali Kaminski,et al.  Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis. , 2006, American journal of respiratory and critical care medicine.

[81]  G. Raghu,et al.  High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis , 2006, European Respiratory Journal.

[82]  M. Jinnin,et al.  Increased expression of integrin alphavbeta5 induces the myofibroblastic differentiation of dermal fibroblasts. , 2006, The American journal of pathology.

[83]  M. Jinnin,et al.  Increased Expression of Integrin αvβ3 Contributes to the Establishment of Autocrine TGF-β Signaling in Scleroderma Fibroblasts1 , 2005, The Journal of Immunology.

[84]  Johny Verschakelen,et al.  High-dose acetylcysteine in idiopathic pulmonary fibrosis. , 2005, The New England journal of medicine.

[85]  J. Myers,et al.  Histopathologic features and outcome of patients with acute exacerbation of idiopathic pulmonary fibrosis undergoing surgical lung biopsy. , 2005, Chest.

[86]  Katsutoshi Nakayama,et al.  Anticoagulant therapy for idiopathic pulmonary fibrosis. , 2005, Chest.

[87]  A. Nicholson,et al.  Induction of Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells by Transforming Growth Factor-β1 : Potential Role in Idiopathic Pulmonary Fibrosis , 2005 .

[88]  R. Johns,et al.  Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis. , 2005, The American journal of pathology.

[89]  M. Kolb,et al.  Progressive transforming growth factor beta1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. , 2005, American journal of respiratory and critical care medicine.

[90]  M. Burdick,et al.  CXCL11 attenuates bleomycin-induced pulmonary fibrosis via inhibition of vascular remodeling. , 2005, American journal of respiratory and critical care medicine.

[91]  P. Oettgen,et al.  Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma. , 2005, The Journal of clinical investigation.

[92]  X. de la Cruz,et al.  Do protein motifs read the histone code? , 2005, BioEssays : news and reviews in molecular, cellular and developmental biology.

[93]  J. Wong,et al.  Reading and Function of a Histone Code Involved in Targeting Corepressor Complexes for Repression , 2005, Molecular and Cellular Biology.

[94]  M. Jinnin,et al.  Increased expression of integrin alpha(v)beta3 contributes to the establishment of autocrine TGF-beta signaling in scleroderma fibroblasts. , 2005, Journal of immunology.

[95]  Michael F Beers,et al.  Surfactant protein C biosynthesis and its emerging role in conformational lung disease. , 2005, Annual review of physiology.

[96]  R. Nusse,et al.  Wnt signaling in disease and in development , 2005, Cell Research.

[97]  Q. Xie,et al.  RETRACTED: TGF-β1 induces alveolar epithelial to mesenchymal transition in vitro , 2004 .

[98]  G. Laurent,et al.  Cardiovascular , Pulmonary and Renal Pathology Severity of Lung Injury in Cyclooxygenase-2-Deficient Mice Is Dependent on Reduced Prostaglandin E 2 Production , 2008 .

[99]  V. Ambrosini,et al.  Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF , 2004, Thorax.

[100]  J. Bonner,et al.  Regulation of PDGF and its receptors in fibrotic diseases. , 2004, Cytokine & growth factor reviews.

[101]  R. Strieter,et al.  Innate immunity dictates cytokine polarization relevant to the development of pulmonary fibrosis. , 2004, The Journal of clinical investigation.

[102]  R. Homer,et al.  Regulation of pulmonary fibrosis by chemokine receptor CXCR3. , 2004, The Journal of clinical investigation.

[103]  D. Madtes,et al.  The FASEB Journal express article 10.1096/fj.03-1492fje. Published online May 20, 2004. IL-13 and IL-1β promote lung fibroblast growth through coordinated up-regulation of PDGF-AA and PDGF-Rα , 2022 .

[104]  P. Hasleton,et al.  Angiogenic cytokines in patients with idiopathic interstitial pneumonia , 2004, Thorax.

[105]  Hideo Sakamoto,et al.  Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10. , 2004, American journal of respiratory cell and molecular biology.

[106]  D. Rifkin,et al.  Integrin αVβ6-mediated activation of latent TGF-β requires the latent TGF-β binding protein-1 , 2004, The Journal of cell biology.

[107]  A. Takeshita,et al.  Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary fibrosis in mice. , 2004, American journal of physiology. Lung cellular and molecular physiology.

[108]  L. Yin,et al.  Butyrate suppresses Cox-2 activation in colon cancer cells through HDAC inhibition. , 2004, Biochemical and biophysical research communications.

[109]  T. Moore,et al.  Protection from Fluorescein Isothiocyanate-Induced Fibrosis in IL-13-Deficient, but Not IL-4-Deficient, Mice Results from Impaired Collagen Synthesis by Fibroblasts1 , 2004, The Journal of Immunology.

[110]  C. Houdayer,et al.  Mutation of SFTPC in infantile pulmonary alveolar proteinosis with or without fibrosing lung disease , 2004, American journal of medical genetics. Part A.

[111]  J. Workman,et al.  In Vitro Targeting Reveals Intrinsic Histone Tail Specificity of the Sin3/Histone Deacetylase and N-CoR/SMRT Corepressor Complexes , 2004, Molecular and Cellular Biology.

[112]  K. Flanders,et al.  Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury. , 2004, The American journal of pathology.

[113]  S. Phan,et al.  Bone marrow-derived progenitor cells in pulmonary fibrosis. , 2004, The Journal of clinical investigation.

[114]  D. Madtes,et al.  IL-13 and IL-1beta promote lung fibroblast growth through coordinated up-regulation of PDGF-AA and PDGF-Ralpha. , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[115]  Q. Xie,et al.  TGF-beta1 induces alveolar epithelial to mesenchymal transition in vitro. , 2004, Life sciences.

[116]  A. Knox,et al.  Transcriptional Regulation of Cyclooxygenase 2 by Bradykinin and Interleukin-1β in Human Airway Smooth Muscle Cells: Involvement of Different Promoter Elements, Transcription Factors, and Histone H4 Acetylation , 2003, Molecular and Cellular Biology.

[117]  C. Ruppert,et al.  Prevention of bleomycin-induced lung fibrosis by aerosolization of heparin or urokinase in rabbits. , 2003, American journal of respiratory and critical care medicine.

[118]  D. Abraham,et al.  The role of connective tissue growth factor, a multifunctional matricellular protein, in fibroblast biology. , 2003, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[119]  R. Trisolini,et al.  Acute exacerbation of idiopathic pulmonary fibrosis: report of a series , 2003, European Respiratory Journal.

[120]  Wolfgang Fischle,et al.  Binary switches and modification cassettes in histone biology and beyond , 2003, Nature.

[121]  D. Sheppard,et al.  Transforming Growth Factor-β-Dependent and -Independent Pathways of Induction of Tubulointerstitial Fibrosis in β6−/− Mice , 2003 .

[122]  R. Chambers Role of coagulation cascade proteases in lung repair and fibrosis , 2003, European Respiratory Journal.

[123]  R. Puri,et al.  Therapeutic Attenuation of Pulmonary Fibrosis Via Targeting of IL-4- and IL-13-Responsive Cells 1 , 2003, The Journal of Immunology.

[124]  M. Stacey,et al.  Identification of Circulating Fibrocytes as Precursors of Bronchial Myofibroblasts in Asthma1 , 2003, The Journal of Immunology.

[125]  M. Peters-Golden,et al.  Prostaglandin E2 inhibits fibroblast to myofibroblast transition via E. prostanoid receptor 2 signaling and cyclic adenosine monophosphate elevation. , 2003, American journal of respiratory cell and molecular biology.

[126]  V. Poletti,et al.  Aberrant Wnt/ (cid:1) -Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis , 2003 .

[127]  E. Morrisey Wnt signaling and pulmonary fibrosis. , 2003, The American journal of pathology.

[128]  Richard J. Stillion,et al.  Analysis of mannose receptor regulation by IL‐4, IL‐10, and proteolytic processing using novel monoclonal antibodies , 2003, Journal of leukocyte biology.

[129]  W. Waldman,et al.  The role of microvascular injury in the evolution of idiopathic pulmonary fibrosis. , 2003, American journal of clinical pathology.

[130]  A. Nicholson,et al.  Interstitial vascularity in fibrosing alveolitis. , 2003, American journal of respiratory and critical care medicine.

[131]  M. Peters-Golden,et al.  Alveolar epithelial cell inhibition of fibroblast proliferation is regulated by MCP-1/CCR2 and mediated by PGE2. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[132]  D. Sheppard,et al.  Transforming growth factor-beta-dependent and -independent pathways of induction of tubulointerstitial fibrosis in beta6(-/-) mice. , 2003, The American journal of pathology.

[133]  V. Poletti,et al.  Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis. , 2003, The American journal of pathology.

[134]  P. Jones,et al.  N-CoR-HDAC corepressor complexes: roles in transcriptional regulation by nuclear hormone receptors. , 2003, Current topics in microbiology and immunology.

[135]  J. Whitsett,et al.  Hydrophobic surfactant proteins in lung function and disease. , 2002, The New England journal of medicine.

[136]  M. Karsdal,et al.  Matrix Metalloproteinase-dependent Activation of Latent Transforming Growth Factor-β Controls the Conversion of Osteoblasts into Osteocytes by Blocking Osteoblast Apoptosis* , 2002, The Journal of Biological Chemistry.

[137]  N. Hattori,et al.  Inducible lung-specific urokinase expression reduces fibrosis and mortality after lung injury in mice. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[138]  M. Burdick,et al.  Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. , 2002, American journal of respiratory cell and molecular biology.

[139]  Hsien-yu Wang,et al.  Activation of the β-Catenin/Lef-Tcf Pathway Is Obligate for Formation of Primitive Endoderm by Mouse F9 Totipotent Teratocarcinoma Cells in Response to Retinoic Acid* , 2002, The Journal of Biological Chemistry.

[140]  J. Stewart,et al.  A rearranged form of Epstein-Barr virus DNA is associated with idiopathic pulmonary fibrosis. , 2002, American journal of respiratory and critical care medicine.

[141]  E. Neilson,et al.  Evidence that fibroblasts derive from epithelium during tissue fibrosis. , 2002, The Journal of clinical investigation.

[142]  K. Kuwano,et al.  References Subscriptions Permissions Email Alerts TGF-β1 as an Enhancer of Fas-Mediated , 2013 .

[143]  Jonathan Haines,et al.  Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. , 2002, American journal of respiratory and critical care medicine.

[144]  D. Warburton,et al.  Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[145]  R. Chambers,et al.  Role of thrombin and its major cellular receptor, protease-activated receptor-1, in pulmonary fibrosis. , 2001, Biochemical Society transactions.

[146]  S. Hampson Randomised, placebo-controlled trial , 2002 .

[147]  M. Burdick,et al.  ENA-78 is an important angiogenic factor in idiopathic pulmonary fibrosis. , 2001, American journal of respiratory and critical care medicine.

[148]  V. Poli,et al.  The Transcription Factor C/EBPβ Is Essential for Inducible Expression of the cox-2 Gene in Macrophages but Not in Fibroblasts* , 2001, The Journal of Biological Chemistry.

[149]  D. Romberger,et al.  Prostaglandin E(2) inhibits fibroblast chemotaxis. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[150]  Liliana Attisano,et al.  Synergistic Cooperation between Hypoxia and Transforming Growth Factor-β Pathways on Human Vascular Endothelial Growth Factor Gene Expression* , 2001, The Journal of Biological Chemistry.

[151]  T. Moore,et al.  Protection from Pulmonary Fibrosis in the Absence of CCR2 Signaling1 , 2001, The Journal of Immunology.

[152]  Allan Balmain,et al.  TGF-β signaling in tumor suppression and cancer progression , 2001, Nature Genetics.

[153]  R. Homer,et al.  Interleukin-13 Induces Tissue Fibrosis by Selectively Stimulating and Activating Transforming Growth Factor β1 , 2001, The Journal of experimental medicine.

[154]  P. Brehm,et al.  Regulation of Neuronal Traits by a Novel Transcriptional Complex , 2001, Neuron.

[155]  N. Goldsack,et al.  Direct thrombin inhibition reduces lung collagen, accumulation, and connective tissue growth factor mRNA levels in bleomycin-induced pulmonary fibrosis. , 2001, The American journal of pathology.

[156]  S. Berger,et al.  Structure and function of bromodomains in chromatin-regulating complexes. , 2001, Gene.

[157]  R. D. du Bois,et al.  Localisation of transforming growth factor β1 and β3 mRNA transcripts in normal and fibrotic human lung , 2001, Thorax.

[158]  E. Gabazza,et al.  Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse. , 2001, American journal of respiratory and critical care medicine.

[159]  A. Wolffe,et al.  Chromatin remodeling and transcriptional activation: the cast (in order of appearance) , 2001, Oncogene.

[160]  K. Subbaramaiah,et al.  Peroxisome proliferator-activated receptor gamma ligands suppress the transcriptional activation of cyclooxygenase-2. Evidence for involvement of activator protein-1 and CREB-binding protein/p300. , 2001, The Journal of biological chemistry.

[161]  G. Laurent,et al.  Cyclooxygenase-2 deficiency results in a loss of the anti-proliferative response to transforming growth factor-beta in human fibrotic lung fibroblasts and promotes bleomycin-induced pulmonary fibrosis in mice. , 2001, The American journal of pathology.

[162]  Eun-Joung Moon,et al.  Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes , 2001, Nature Medicine.

[163]  O. Eickelberg,et al.  Molecular mechanisms of TGF‐β antagonism by interferon γ and cyclosporine A in lung fibroblasts , 2001 .

[164]  F. Askin,et al.  A mutation in the surfactant protein C gene associated with familial interstitial lung disease. , 2001, The New England journal of medicine.

[165]  S. Schreiber,et al.  CoREST is an integral component of the CoREST- human histone deacetylase complex. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[166]  O. Eickelberg,et al.  Molecular mechanisms of TGF-(beta) antagonism by interferon (gamma) and cyclosporine A in lung fibroblasts. , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[167]  A. Balmain,et al.  TGF-β signaling in tumor suppression and cancer progression , 2001, Nature Genetics.

[168]  K. Chida,et al.  Relevance of tissue factor and tissue factor pathway inhibitor for hypercoagulable state in the lungs of patients with idiopathic pulmonary fibrosis. , 2000, Thrombosis research.

[169]  D. Sterner,et al.  Acetylation of Histones and Transcription-Related Factors , 2000, Microbiology and Molecular Biology Reviews.

[170]  Y. Kaneda,et al.  Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[171]  I. Stamenkovic,et al.  Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. , 2000, Genes & development.

[172]  M. Burdick,et al.  IFN-gamma-inducible protein-10 attenuates bleomycin-induced pulmonary fibrosis via inhibition of angiogenesis. , 1999, Journal of immunology.

[173]  Qingjian Wang,et al.  Reduction of bleomycin induced lung fibrosis by transforming growth factor β soluble receptor in hamsters , 1999, Thorax.

[174]  M. Anderson,et al.  CoREST: a functional corepressor required for regulation of neural-specific gene expression. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[175]  M. Kitagawa,et al.  An F‐box protein, FWD1, mediates ubiquitin‐dependent proteolysis of β‐catenin , 1999, The EMBO journal.

[176]  A. Woodcock,et al.  The detection of Epstein-Barr virus DNA in lung tissue from patients with idiopathic pulmonary fibrosis. , 1999, American journal of respiratory and critical care medicine.

[177]  R. Homer,et al.  Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. , 1999, The Journal of clinical investigation.

[178]  N. Kaminski,et al.  The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. , 1999, Cell.

[179]  N. Hattori,et al.  Upregulation of fibrinolysis by adenovirus-mediated transfer of urokinase-type plasminogen activator genes to lung cells in vitro and in vivo. , 1999, Human gene therapy.

[180]  D. Sheppard,et al.  Expression of the human integrin beta6 subunit in alveolar type II cells and bronchiolar epithelial cells reverses lung inflammation in beta6 knockout mice. , 1998, American journal of respiratory cell and molecular biology.

[181]  P. Zipfel,et al.  Increased expression of proinflammatory chemokines in bronchoalveolar lavage cells of patients with progressing idiopathic pulmonary fibrosis and sarcoidosis. , 1998, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[182]  J. Myers,et al.  Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. , 1998, American journal of respiratory and critical care medicine.

[183]  T. Tanabe,et al.  Transcriptional role of the nuclear factor kappa B site in the induction by lipopolysaccharide and suppression by dexamethasone of cyclooxygenase-2 in U937 cells. , 1998, Biochemical and biophysical research communications.

[184]  Akira Kikuchi,et al.  Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK‐3β and β‐catenin and promotes GSK‐3β‐dependent phosphorylation of β‐catenin , 1998 .

[185]  A. Mann,et al.  Predictive value of response to treatment of T-lymphocyte subpopulations in idiopathic pulmonary fibrosis. , 1998, The European respiratory journal.

[186]  R. Hubbard,et al.  Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study. , 1998, Chest.

[187]  A. Kikuchi,et al.  Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. , 1998, The EMBO journal.

[188]  J. Fujita,et al.  The role of neutrophils in the pathogenesis of idiopathic pulmonary fibrosis. , 1997, Chest.

[189]  K. Csaky,et al.  Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. , 1997, The Journal of clinical investigation.

[190]  R. Whyte,et al.  The CXC chemokines, IL-8 and IP-10, regulate angiogenic activity in idiopathic pulmonary fibrosis. , 1997, Journal of immunology.

[191]  T. Urano,et al.  Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. , 1997, American journal of respiratory and critical care medicine.

[192]  M. Yamakido,et al.  Effects of neutrophil elastase inhibitor on bleomycin-induced pulmonary fibrosis in mice. , 1997, American journal of respiratory and critical care medicine.

[193]  R. D. du Bois,et al.  Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis. , 1997, The American journal of pathology.

[194]  D. Sheppard,et al.  Differential regulation of airway epithelial integrins by growth factors. , 1996, American journal of respiratory cell and molecular biology.

[195]  R. Hubbard,et al.  Occupational exposure to metal or wood dust and aetiology of cryptogenic fibrosing alveolitis , 1996, The Lancet.

[196]  R. D. McCoy,et al.  Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene. , 1996, Journal of Clinical Investigation.

[197]  R. Chambers,et al.  Role of thrombin in pulmonary fibrosis , 1995, The Lancet.

[198]  David J. Anderson,et al.  Silencing is golden: negative regulation in the control of neuronal gene transcription , 1995, Current Opinion in Neurobiology.

[199]  D. Lamb,et al.  A type 2 (Th2‐like) pattern of immune response predominates in the pulmonary interstitium of patients with cryptogenic fibrosing alveolitis (CFA) , 1995, Clinical and experimental immunology.

[200]  G. Laurent,et al.  Interleukin-8. Differential expression in lone fibrosing alveolitis and systemic sclerosis. , 1995, American journal of respiratory and critical care medicine.

[201]  T. Urano,et al.  Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. , 1995, Thrombosis research.

[202]  G. Gurujeyalakshmi,et al.  Molecular mechanisms of antifibrotic effect of interferon gamma in bleomycin-mouse model of lung fibrosis: downregulation of TGF-beta and procollagen I and III gene expression. , 1995, Experimental lung research.

[203]  R. Bucala,et al.  Circulating Fibrocytes Define a New Leukocyte Subpopulation That Mediates Tissue Repair , 1994, Molecular medicine.

[204]  H. Herschman,et al.  v-src induction of the TIS10/PGS2 prostaglandin synthase gene is mediated by an ATF/CRE transcription response element , 1994, Molecular and cellular biology.

[205]  G. Sempowski,et al.  Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors. Role of IL-4 in enhancing fibroblast proliferation and collagen synthesis. , 1994, Journal of immunology.

[206]  F. Meloni,et al.  Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. , 1994, American journal of respiratory and critical care medicine.

[207]  M. Peão,et al.  Neoformation of blood vessels in association with rat lung fibrosis induced by bleomycin , 1994, The Anatomical record.

[208]  K. Aisaka,et al.  Effects of gamma-interferon on collagen and histamine content in bleomycin-induced lung fibrosis in rats. , 1993, Lymphokine and cytokine research.

[209]  G. Grau,et al.  Effective treatment of the pulmonary fibrosis elicited in mice by bleomycin or silica with anti-CD-11 antibodies. , 1993, The American review of respiratory disease.

[210]  J. Taipale,et al.  Release of transforming growth factor-beta 1 from the pericellular matrix of cultured fibroblasts and fibrosarcoma cells by plasmin and thrombin. , 1992, The Journal of biological chemistry.

[211]  A. J. Valente,et al.  Expression of monocyte chemoattractant protein 1 mRNA in human idiopathic pulmonary fibrosis. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[212]  G. Raghu,et al.  Effect of γ-Interferon on Collagen Synthesis by Normal and Fibrotic Human Lung Fibroblasts , 1992 .

[213]  J. Parrish,et al.  Cyclic-adenosine monophosphate (cAMP) is elevated during capacitation of bovine sperm by heparin or oviduct fluid , 1992 .

[214]  G. Raghu,et al.  Effect of gamma-interferon on collagen synthesis by normal and fibrotic human lung fibroblasts. , 1992, Chest.

[215]  T. Colby,et al.  Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[216]  K. Sekizawa,et al.  Prognosis of idiopathic pulmonary fibrosis in patients with mucous hypersecretion. , 1991, The American review of respiratory disease.

[217]  M. Kitaichi,et al.  In vitro production of B cell growth factor and B cell differentiation factor by peripheral blood mononuclear cells and bronchoalveolar lavage T lymphocytes from patients with idiopathic pulmonary fibrosis , 1990, Clinical and experimental immunology.

[218]  B. Bresnihan,et al.  Bronchoalveolar lavage in patients with mild and severe rheumatoid lung disease. , 1990, Thorax.

[219]  F. Lemaire,et al.  Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. , 1990, The New England journal of medicine.

[220]  W. Carter,et al.  Effects of interferon-gamma on expression of cell surface receptors for collagen and deposition of newly synthesized collagen by cultured human lung fibroblasts. , 1989, The Journal of clinical investigation.

[221]  J. Elias Tumor necrosis factor interacts with interleukin-1 and interferons to inhibit fibroblast proliferation via fibroblast prostaglandin-dependent and -independent mechanisms. , 1988, The American review of respiratory disease.

[222]  Gary R. Grotendorst,et al.  Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis. , 1987, The New England journal of medicine.

[223]  M. Schwarz,et al.  Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy. , 1987, The American review of respiratory disease.

[224]  H. Chapman,et al.  Abnormalities in pathways of alveolar fibrin turnover among patients with interstitial lung disease. , 1986, The American review of respiratory disease.

[225]  V. Ferrans,et al.  Intraluminal fibrosis in interstitial lung disorders. , 1986, The American journal of pathology.

[226]  S. Phan,et al.  The effects of the nude (nu/nu) mutation on bleomycin-induced pulmonary fibrosis. A biochemical evaluation. , 1983, The American review of respiratory disease.

[227]  J. Clark,et al.  Bleomycin-induced pulmonary fibrosis in hamsters: effect of neutrophil depletion on lung collagen synthesis. , 1982, The American review of respiratory disease.

[228]  P. Ward,et al.  The development of bleomycin-induced pulmonary fibrosis in neutrophil-depleted and complement-depleted rats. , 1981, The American journal of pathology.

[229]  R. Rudd,et al.  Cryptogenic fibrosing alveolitis. Relationships of pulmonary physiology and bronchoalveolar lavage to response to treatment and prognosis. , 1981, The American review of respiratory disease.

[230]  P. Ward,et al.  Bleomycin-induced pulmonary fibrosis in the rat: inhibition by indomethacin. , 1979, The American journal of pathology.

[231]  P. Choubrac,et al.  Bleomycin induced pulmonary fibrosis , 1976 .

[232]  M. Turner‐Warwick SYSTEMIC ARTERIAL PATTERNS IN THE LUNG AND CLUBBING OF THE FINGERS. , 1963, Thorax.

[233]  L. Woolner,et al.  Pulmonary fibrosis. , 1954, The Medical clinics of North America.