Oxidative stress and the pathogenesis of scleroderma: the Murrell's hypothesis revisited.
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.
Gabrielli
Armando
A
Dipartimento di Scienze Mediche e Chirurgiche, Clinica Medica, Università Politecnica delle Marche, Ancona, Italy. a.gabrielli@univpm.it
Svegliati
Silvia
S
Moroncini
Gianluca
G
Pomponio
Giovanni
G
Santillo
Mariarosaria
M
Avvedimento
Enrico V
EV
D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000009:adverse effects*; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology; D012595:Scleroderma, Systemic / Q000209:etiology* / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology
D001323:Autoantibodies; D001324:Autoantigens; D017382:Reactive Oxygen Species; D017479:Receptors, Platelet-Derived Growth Factor