New insights into the role of oxidative stress in scleroderma fibrosis

Abstract

Systemic sclerosis (Scleroderma - SSc) is a connective tissue disorder of unknown aetiology characterized by extensive fibrosis of the skin and visceral organs, by vascular abnormalities and immunological manifestations.Recent evidence suggest that the cellular redox state may play a significant role in the progression of scleroderma fibrosis. Mechanisms involved include an autoamplification circuit linking ROS, Ras and ERK 1-2 which in turn amplifies and maintains the autocrine loop made up by cytokines, growth factors and their cognate receptors.This review summarizes the recent progress on the role of oxidative stress in the pathophysiology of scleroderma and disorders characterised by organ fibrosis.

Keywords: Systemic sclerosis; fibrosis.; free radicals.

Fig. (1)

The vicious biochemical cycle that leads to excessive oxidative stress in vessel wall following persistent vascular injury, and to fibrosis (adapted from FÖrstermann and Münzel: Circulation 2006; 113: 1708-1714). Inactivation of MKPs (MAPK phosphatases) is responsible for activation of MAPKs.