TGF-beta signaling and the fibrotic response.
The cause of fibrotic diseases, pathologies characterized by excessive production, deposition, and contraction of extracellular matrix, is unknown. To understand the molecular basis of fibrotic disease, it is essential to appreciate how matrix deposition is normally controlled and how this process is dysregulated in fibrogenesis. This review discusses the current state of knowledge concerning interactions among the profibrotic proteins transforming growth factor-beta (TGF-beta), connective tissue growth factor (CTGF, CCN2), and ED-A fibronectin (ED-A FN) and the antifibrotic proteins tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (IFN-gamma).
Leask
Andrew
A
Centre for Rheumatology, Department of Medicine, Royal Free & University College Medical School, Rowland Hill St., London, UK NW3 2PF. a.leask@rfc.ucl.ac.uk
Abraham
David J
DJ
D000818:Animals; D055513:Connective Tissue Growth Factor; D004268:DNA-Binding Proteins / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005353:Fibronectins / Q000502:physiology; D005355:Fibrosis / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D015398:Signal Transduction; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
C526317:CCN2 protein, human; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D055513:Connective Tissue Growth Factor; D007371:Interferon-gamma