title: Molecular targets in pulmonary fibrosis: the myofibroblast in focus.
abstract: Idiopathic pulmonary fibrosis (IPF) is one of a group of interstitial lung diseases that are characterized by excessive matrix deposition and destruction of the normal lung architecture. Long-term survival of IPF patients is poor, with a 5-year survival rate of only 20%. Despite a lack of evidence-based benefit, IPF has historically been treated with corticosteroids and/or cytotoxic agents such as prednisone. Given the poor efficacy of these drugs, novel therapeutic strategies are required for the management of IPF. This demands a better understanding of the molecular mechanisms underlying the pathogenesis and progression of this disease. The primary effector cell in fibrosis is the myofibroblast; these cells are highly synthetic for collagen, have a contractile phenotype, and are characterized by the presence of alpha-smooth muscle actin stress fibers. They may be derived by activation/proliferation of resident lung fibroblasts, epithelial-mesenchymal differentiation, or recruitment of circulating fibroblastic stem cells (fibrocytes). From a therapeutic viewpoint, interfering with the pathways that lead to myofibroblast expansion should be of considerable benefit in the treatment of IPF. This review will highlight some of the key molecules involved in this process and the clinical trials that have ensued.
authors.affiliation: Centre for Respiratory Research, University College London, Rayne Institute, London, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Scotton
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Chambers
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D054377:Chemokine CXCL12 / Q000502:physiology; D055513:Connective Tissue Growth Factor; D018450:Disease Progression; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D018793:Interleukin-13 / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011658:Pulmonary Fibrosis / Q000175:diagnosis / Q000503:physiopathology*; D044463:Receptor, PAR-1 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
chemical_list: C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D010982:Platelet-Derived Growth Factor; D044463:Receptor, PAR-1; D019718:Receptors, CXCR4; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D055513:Connective Tissue Growth Factor