期刊
JOURNAL OF CLINICAL MEDICINE
卷 10, 期 20, 页码 -出版社
MDPI
DOI: 10.3390/jcm10204791
关键词
fibrosis; systemic sclerosis; oxidative stress; reactive oxygen species; NADPH; NOX4
资金
- NIH [AR 19616]
- Scleroderma Research Fund from Thomas Jefferson University
Excessive oxidative stress caused by high levels of ROS has been implicated in the development of fibrosis in SSc, with NOX4 being suggested as a potential therapeutic target. The involvement of NOX4 in the production of fibrotic proteins and ROS, as well as its potential role in endothelial and vascular abnormalities, suggests it as a novel target for treating SSc.
Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently progressive fibrotic process in Systemic Sclerosis (SSc). The role of excessive oxidative stress in SSc pathogenesis has been supported by the demonstration of increased levels of numerous biomarkers, indicative of cellular and molecular oxidative damage in serum, plasma, and other biological fluids from SSc patients, and by the demonstration of elevated production of ROS by various cell types involved in the SSc fibrotic process. However, the precise mechanisms mediating oxidative stress development in SSc and its pathogenetic effects have not been fully elucidated. The participation of the NADPH oxidase NOX4, has been suggested and experimentally supported by the demonstration that SSc dermal fibroblasts display constitutively increased NOX4 expression and that reduction or abrogation of NOX4 effects decreased ROS production and the expression of genes encoding fibrotic proteins. Furthermore, NOX4-stimulated ROS production may be involved in the development of certain endothelial and vascular abnormalities and may even participate in the generation of SSc-specific autoantibodies. Collectively, these observations suggest NOX4 as a novel therapeutic target for SSc.
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