title: Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.
abstract: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed.
authors.affiliation: Scleroderma Center, Thomas Jefferson University, 233 South 10th Street, Suite 509 BLSB, Philadelphia, PA, 19107, USA.
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Piera-Velazquez
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Jimenez
mesh_terms: D016922:Cellular Senescence / Q000502:physiology*; D005355:Fibrosis; D006801:Humans; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000473:pathology* / Q000503:physiopathology
chemical_list: D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human