title: The role of TGF-beta signaling in the pathogenesis of fibrosis in scleroderma.
abstract: Excessive extracellular matrix (ECM) deposition in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). The pathogenesis of SSc is still poorly understood, but increasing evidence suggests that transforming growth factor (TGF)-beta is a key mediator of tissue fibrosis as a consequence of ECM accumulation in pathological states such as systemic sclerosis. TGF-beta regulates diverse biological activities including cell growth, cell death or apoptosis, cell differentiation, and ECM synthesis. TGF-beta is known to induce the expression of ECM proteins in mesenchymal cells and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. This review focuses on the possible role of TGF-beta in the pathogenesis of fibrosis in SSc.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. IN-DER@h.u-tokyo.ac.jp
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
mesh_terms: D055513:Connective Tissue Growth Factor; D004268:DNA-Binding Proteins / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D012595:Scleroderma, Systemic / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D015398:Signal Transduction; D051785:Smad Proteins; D015534:Trans-Activators / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: C526317:CCN2 protein, human; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D020928:Mitogen-Activated Protein Kinases