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The ubiquitin proteasome system as a potential therapeutic target for systemic sclerosis

  • Silke Meiners
    Correspondence
    Reprint requests: Silke Meiners, Helmholtz Zentrum München, Comprehensive Pneumology Center, Max-Lebsche-Platz 31, 81377 München, Germany;
    Affiliations
    Comprehensive Pneumology Center (CPC), University Hospital, Ludwig Maximilians University, Helmholtz Zentrum München, Germany

    Comprehensive Pneumology Center, Munich (CPC-M), Germany

    Member of the German Center for Lung Research (DZL), Munich, Germany
    Search for articles by this author
  • John Evankovich
    Affiliations
    Pulmonary, Allergy, and Critical Care Medicine, Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
    Search for articles by this author
  • Rama K. Mallampalli
    Correspondence
    Reprint requests: Rama K. Mallampalli, Pulmonary, Allergy, & Critical Care Medicine, Department of Medicine, University of Pittsburgh, UPMC Montefiore, NW 628, Pittsburgh, PA 15213;
    Affiliations
    Pulmonary, Allergy, and Critical Care Medicine, Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA

    Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA
    Search for articles by this author
Published:March 29, 2018DOI:https://doi.org/10.1016/j.trsl.2018.03.003
      The present review aims to summarize available knowledge on the role of the ubiquitin-proteasome system (UPS) in the pathogenesis of scleroderma and scleroderma-related disease mechanisms. This will provide the reader with a more mechanistic understanding of disease pathogenesis and help to identify putative novel targets within the UPS for potential therapeutic intervention. Because of the heterogenous manifestations of scleroderma, we will primarily focus on conserved mechanisms that are involved in the development of lung scleroderma phenotypes.

      Abbreviations:

      SSc (Systemic Sclerosis), ILD (Interstitial Lung Disease), ECM (Extracellular Matrix), MHC (Major Histocompatibility Complex), ATP (Adenosine Triphosphate), TGFβ (transforming growth factor β), SCFFBXL2 (Skp-Cullin-F box (SCF) FBXL2), RNF216 (RING Finger Protein (RNF) 216), GM-CSF (Granulocyte-macrophage colony-stimulating factor), TNF (tumor necrosis factor), IFN (interferon), IL (interleukin), PRRs (Pattern recognition receptors), TLR (Toll-like receptor)
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