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Oxidative stress and the pathogenesis of scleroderma: the Murrell’s hypothesis revisited

Abstract

Systemic sclerosis (SSc, scleroderma) is a devastating, immune-mediated, multisystem disorder characterized by microvasculature damage, circulating autoantibodies, and fibroblast activation, leading to massive fibrosis of skin, vessels, muscles, and visceral organs. Scleroderma causes disability and death as the result of end-stage organ failure. At present, no specific diagnostic nor therapeutic tools are available to handle the disease. In spite of significant effort, the etiology and pathogenesis of SSc remain obscure and, consequently, the disease outcome is unpredictable. Several years ago, Murrell suggested a unifying hypothesis linking the pathogenesis of scleroderma to the generation of a large excess of reactive oxygen species. This hypothesis has been substantiated by several reports indicating the presence of an abnormal redox state in patients with scleroderma. This review will summarize the available evidence supporting the link between free radicals and the main pathological features of scleroderma.

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Acknowledgments

This work has been supported in part by A.I.L.S. (Associazione Italiana per la Lotta alla Sclerodermia), the Ministero Italiano per l’Università e la Ricerca Scientifica (MIUR 2006), and a generous grant from Fondazione Cariverona.

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Correspondence to Armando Gabrielli.

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Gabrielli, A., Svegliati, S., Moroncini, G. et al. Oxidative stress and the pathogenesis of scleroderma: the Murrell’s hypothesis revisited. Semin Immunopathol 30, 329–337 (2008). https://doi.org/10.1007/s00281-008-0125-4

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Keywords

  • Oxidative stress
  • Tissue fibrosis
  • Systemic sclerosis
  • Autoantibodies to PDGF receptor