Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression

In response to tissue stiffening, fibroblasts increase production of extracellular matrix while decreasing production of matrix-degrading enzymes and the fibrosis inhibitor prostaglandin E2.

• Publication year

  2010

• Venue

  Journal of Cell Biology

• Publication date

  2010-08-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.201004082PMID 20733059PMCID 2928007
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• 16,16-Dimethyl prostaglandin E2 efficacy on prevention and protection from bleomycin-induced lung injury and fibrosis.

  2009cited by this paper
• Prostaglandin F2α receptor signaling facilitates bleomycin-induced pulmonary fibrosis independently of transforming growth factor-β

  2009cited by this paper
• Prostaglandin E2 inhibits the proliferation of human gingival fibroblasts via the EP2 receptor and Epac

  2009cited by this paper
• Prostaglandins and Other Lipid Mediators elecoxib exacerbates hepatic fibrosis and induces hepatocellular ecrosis in rats treated with porcine serum

  2009cited by this paper
• Defective Histone Acetylation Is Responsible for the Diminished Expression of Cyclooxygenase 2 in Idiopathic Pulmonary Fibrosis

  2009cited by this paper
• Vascular smooth muscle cell durotaxis depends on substrate stiffness gradient strength.

  2009cited by this paper
• Mechanically Activated Integrin Switch Controls α5β1 Function

  2009cited by this paper
• Cardiovascular , Pulmonary and Renal Pathology Severity of Lung Injury in Cyclooxygenase-2-Deficient Mice Is Dependent on Reduced Prostaglandin E 2 Production

  2008cited by this paper
• Cellular and molecular mechanisms of fibrosis

  2008cited by this paper
• Growth control by intracellular tension and extracellular stiffness.

  2008cited by this paper
• The role of matrix stiffness in regulating cell behavior

  2008cited by this paper
• Eicosanoid lipid mediators in fibrotic lung diseases: ready for prime time?

  2008cited by this paper
• The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak

  2008influential reference
• Faculty Opinions recommendation of Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix.

  2008influential reference
• Murine models of pulmonary fibrosis.

  2008cited by this paper
• Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix

  2007cited by this paper
• Prostaglandin E(2) inhibits collagen expression and proliferation in patient-derived normal lung fibroblasts via E prostanoid 2 receptor and cAMP signaling.

  2007cited by this paper
• The myofibroblast: one function, multiple origins.

  2007cited by this paper
• Transforming growth factor‐β and substrate stiffness regulate portal fibroblast activation in culture

  2007influential reference
• PGE(2) inhibition of TGF-beta1-induced myofibroblast differentiation is Smad-independent but involves cell shape and adhesion-dependent signaling.

  2007cited by this paper
• Acute exacerbations of idiopathic pulmonary fibrosis.

  2007cited by this paper
• Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis.

  2007cited by this paper
• Three‐dimensional investigation and scoring of extracellular matrix remodeling during lung fibrosis using multiphoton microscopy

  2007cited by this paper
• Cell shape regulates global histone acetylation in human mammary epithelial cells.

  2007cited by this paper
• Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)‐β1–induced collagen synthesis

  2007cited by this paper
• Transforming growth factor-beta receptor type 1 (TGFbetaRI) kinase activity but not p38 activation is required for TGFbetaRI-induced myofibroblast differentiation and profibrotic gene expression.

  2006influential reference
• Focal adhesion size controls tension-dependent recruitment of α-smooth muscle actin to stress fibers

  2006influential reference
• COX-2-derived prostacyclin protects against bleomycin-induced pulmonary fibrosis.

  2006cited by this paper
• [Cellular and molecular mechanisms of fibrosis].

  2006cited by this paper
• Matrix elasticity directs stem cell lineage specification.

  2006cited by this paper
• Transforming Growth Factor-β Receptor Type 1 (TGFβRI) Kinase Activity but Not p38 Activation Is Required for TGFβRI-Induced Myofibroblast Differentiation and Profibrotic Gene Expression

  2006influential reference
• Effect of celecoxib on experimental liver fibrosis in rat

  2006cited by this paper
• Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion.

  2005cited by this paper
• Tensional homeostasis and the malignant phenotype.

  2005influential reference
• Directional persistence of EGF-induced cell migration is associated with stabilization of lamellipodial protrusions.

  2005cited by this paper
• Myosin Phosphatase and Cofilin Mediate cAMP/cAMP-dependent Protein Kinase-induced Decline in Endothelial Cell Isometric Tension and Myosin II Regulatory Light Chain Phosphorylation*

  2005cited by this paper
• The Clinical Course of Patients with Idiopathic Pulmonary Fibrosis

  2005cited by this paper
• Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion

  2005cited by this paper
• Pivotal role of cathepsin K in lung fibrosis.

  2004cited by this paper
• Cyclooxygenase-2 is up-regulated in lung parenchyma of chronic obstructive pulmonary disease and down-regulated in idiopathic pulmonary fibrosis.

  2004influential reference
• The lung as a privileged site for the beneficial actions of PGE2.

  2004cited by this paper
• Elasticity of native and cross-linked polyelectrolyte multilayer films.

  2004cited by this paper
• Selected Contribution: Airway contractility and smooth muscle Ca2+ signaling in lung slices from different mouse strains

  2003cited by this paper
• Directed Movement of Vascular Smooth Muscle Cells on Gradient-Compliant Hydrogels†

  2003influential reference
• Normal and Pathologic Soft Tissue Remodeling: Role of the Myofibroblast, with Special Emphasis on Liver and Kidney Fibrosis

  2003cited by this paper
• Prostaglandin E2 inhibits fibroblast to myofibroblast transition via E. prostanoid receptor 2 signaling and cyclic adenosine monophosphate elevation.

  2003cited by this paper
• Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially mediated by phosphorylation of RhoA.

  2003cited by this paper
• Airway contractility and smooth muscle Ca(2+) signaling in lung slices from different mouse strains.

  2003cited by this paper
• Prostaglandin E2 synthesis and suppression of fibroblast proliferation by alveolar epithelial cells is cyclooxygenase-2-dependent.

  2002cited by this paper
• Myofibroblasts and mechano-regulation of connective tissue remodelling

  2002influential reference
• Susceptibility of cyclooxygenase-2-deficient mice to pulmonary fibrogenesis.

  2002cited by this paper
• 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.

  2001influential reference
• Idiopathic pulmonary fibrosis.

  2001cited by this paper
• Idiopathic Pulmonary Fibrosis: Prevailing and Evolving Hypotheses about Its Pathogenesis and Implications for Therapy

  2001cited by this paper
• Fibroblast Quiescence in Floating or Released Collagen Matrices

  2001cited by this paper
• Changes in extracellular matrix and tissue viscoelasticity in bleomycin-induced lung fibrosis. Temporal aspects.

  2000cited by this paper
• Substrate flexibility regulates growth and apoptosis of normal but not transformed cells.

  2000influential reference
• Cell movement is guided by the rigidity of the substrate.

  2000cited by this paper
• Different Expression of TNF- α Receptors and Prostaglandin E2Production in Normal and Fibrotic Lung Fibroblasts

  2000cited by this paper
• Different expression of TNF-alpha receptors and prostaglandin E(2 )Production in normal and fibrotic lung fibroblasts: potential implications for the evolution of the inflammatory process.

  2000cited by this paper
• The compliance of collagen gels regulates transforming growth factor-β induction of α-smooth muscle actin in fibroblasts

  1999influential reference
• The compliance of collagen gels regulates transforming growth factor-beta induction of alpha-smooth muscle actin in fibroblasts.

  1999influential reference
• Role of EP2 receptors and cAMP in prostaglandin E2 regulated expression of type I collagen α1, lysyl oxidase, and cyclooxygenase‐1 genes in human embryo lung fibroblasts

  1998cited by this paper
• cAMP-induced Morphological Changes Are Counteracted by the Activated RhoA Small GTPase and the Rho Kinase ROKα*

  1998cited by this paper
• Cell locomotion and focal adhesions are regulated by substrate flexibility.

  1997cited by this paper
• Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes.

  1996cited by this paper
• Regulation of fibroblast procollagen production. Transforming growth factor-beta 1 induces prostaglandin E2 but not procollagen synthesis via a pertussis toxin-sensitive G-protein.

  1995cited by this paper
• Cultured lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis have a diminished capacity to synthesize prostaglandin E2 and to express cyclooxygenase-2.

  1995influential reference
• Thermal and ambient-induced deflections of scanning force microscope cantilevers

  1994cited by this paper
• Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study.

  1994influential reference
• Poisson's ratio in polymer gels near the phase-transition point.

  1993influential reference
• Augmentation of functional prostaglandin E levels on the respiratory epithelial surface by aerosol administration of prostaglandin E.

  1991cited by this paper
• The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis.

  1991cited by this paper
• Transforming growth factor-beta stimulation of lung fibroblast prostaglandin E2 production.

  1989cited by this paper
• Cyclooxygenase metabolites are compartmentalized in the human lower respiratory tract.

  1987influential reference
• Poissons' ratio of lung parenchyma and parenchymal interaction with bronchi.

  1986influential reference
• Mechanical analysis of hypertrophic scar tissue: structural basis for apparent increased rigidity.

  1986cited by this paper
• Fibroblast prostaglandin E2 synthesis. Persistence of an abnormal phenotype after short-term exposure to mononuclear cell products.

  1983cited by this paper
• The mechanism of exercise-induced R-wave amplitude changes in coronary heart disease. Still controversial.

  1982cited by this paper
• A model for mechanical structure of the alveolar duct.

  1982cited by this paper
• Lung tissue resistance in diffuse interstitial pulmonary fibrosis.

  1967cited by this paper

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  2026cites this paper
• Fibroblasts as regulators of lung immunity, repair and fibrosis.

  2026cites this paper
• Spatial transcriptomics reveals altered communities and drivers of aberrant epithelia and pro-fibrotic fibroblasts in interstitial lung diseases.

  2026cites this paper
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  2026cites this paper
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  2026cites this paper
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  2026cites this paper
• The importance of mechanical forces in chronic respiratory diseases.

  2026cites this paper
• FAK modulates immune response and fibroblast activation in biomaterial-induced fibrosis.

  2026cites this paper
• Modelling the Squishy Effect in Interstitial Pulmonary Fibrosis

  2025cites this paper
• Aging and Intestinal Fibrosis: Mechanisms, Implications, and Therapeutic Strategies

  2025influential citation
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  2025cites this paper
• Mechanobiology of Adipose Tissue Remodeling.

  2025cites this paper
• Matrix stiffness induces heritable changes in chromosome numbers, consistent with solid tumor heterogeneity

  2025cites this paper
• The role of epigenetic regulation in idiopathic pulmonary fibrosis.

  2025cites this paper
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  2025cites this paper
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