Redox-fibrosis: Impact of TGFβ1 on ROS generators, mediators and functional consequences

• Oxidative stress can be both a cause or a consequence of fibrotic events.
• TGF-β1 is a key cytokine which contributes to production and reduction of ROS.
• Feedback: ROS are able to activate TGF-β1.
• ROS are powerful post-transcriptional and epigenetic regulators in fibrosis.
• Are antioxidants a treatment option during fibrosis?

Fibrosis is one of the most prevalent features of age-related diseases like obesity, diabetes, non-alcoholic fatty liver disease, chronic kidney disease, or cardiomyopathy and affects millions of people in all countries. Although the understanding about the pathophysiology of fibrosis has improved a lot during the recent years, a number of mechanisms still remain unknown. Although TGF-β1 signaling, loss of metabolic homeostasis and chronic low-grade inflammation appear to play important roles in the pathogenesis of fibrosis, recent evidence indicates that oxidative stress and the antioxidant system may also be crucial for fibrosis development and persistence. These findings point to a concept of a redox-fibrosis where the cellular oxidant and antioxidant system could be potential therapeutic targets. The current review aims to summarize the existing links between TGF-β1 signaling, generation and action of reactive oxygen species, expression of antioxidative enzymes, and functional consequences including epigenetic redox-mediated responses during fibrosis.

Figure optionsDownload as PowerPoint slide