Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target
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...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/10/20/4791 |
| _version_ | 1797514229759082496 |
|---|---|
| author | Sonsoles Piera-Velazquez Sergio A. Jimenez |
| author_facet | Sonsoles Piera-Velazquez Sergio A. Jimenez |
| author_sort | Sonsoles Piera-Velazquez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:28:40Z |
| format | Article |
| id | doaj.art-3221c03ecedf48fe994eee0387d004bf |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T06:28:40Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-3221c03ecedf48fe994eee0387d004bf2023-11-22T18:43:22ZengMDPI AGJournal of Clinical Medicine2077-03832021-10-011020479110.3390/jcm10204791Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic TargetSonsoles Piera-Velazquez0Sergio A. Jimenez1Jefferson Institute of Molecular Medicine and Scleroderma Center, Thomas Jefferson University, Philadelphia, PA 19107, USAJefferson Institute of Molecular Medicine and Scleroderma Center, Thomas Jefferson University, Philadelphia, PA 19107, USANumerous 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.https://www.mdpi.com/2077-0383/10/20/4791fibrosissystemic sclerosisoxidative stressreactive oxygen speciesNADPHNOX4 |
| spellingShingle | Sonsoles Piera-Velazquez Sergio A. Jimenez Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target Journal of Clinical Medicine fibrosis systemic sclerosis oxidative stress reactive oxygen species NADPH NOX4 |
| title | Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target |
| title_full | Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target |
| title_fullStr | Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target |
| title_full_unstemmed | Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target |
| title_short | Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target |
| title_sort | oxidative stress induced by reactive oxygen species ros and nadph oxidase 4 nox4 in the pathogenesis of the fibrotic process in systemic sclerosis a promising therapeutic target |
| topic | fibrosis systemic sclerosis oxidative stress reactive oxygen species NADPH NOX4 |
| url | https://www.mdpi.com/2077-0383/10/20/4791 |
| work_keys_str_mv | AT sonsolespieravelazquez oxidativestressinducedbyreactiveoxygenspeciesrosandnadphoxidase4nox4inthepathogenesisofthefibroticprocessinsystemicsclerosisapromisingtherapeutictarget AT sergioajimenez oxidativestressinducedbyreactiveoxygenspeciesrosandnadphoxidase4nox4inthepathogenesisofthefibroticprocessinsystemicsclerosisapromisingtherapeutictarget |