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Regulation of Wound Healing by the NRF2 Transcription Factor-More Than Cytoprotection
1Institute for Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zürich, 8093 Zurich, Switzerland. paul.hiebert@biol.ethz.ch.
Abstract:
The nuclear factor-erythroid 2-related factor 2 (NRF2) transcription factor plays a central role in mediating the cellular stress response. Due to their antioxidant properties, compounds activating NRF2 have received much attention as potential medications for disease prevention, or even for therapy. Accumulating evidence suggests that activation of the NRF2 pathway also has a major impact on wound healing and may be beneficial in the treatment of chronic wounds, which remain a considerable health and economic burden. While NRF2 activation indeed shows promise, important considerations need to be made in light of corresponding evidence that also points towards pro-tumorigenic effects of NRF2. In this review, we discuss the evidence to date, highlighting recent advances using gain- and loss-of-function animal models and how these data fit with observations in humans.
Insights
Nuclear factor-erythroid 2-related factor 2 (NRF2) activation shows promise for chronic wound healing due to antioxidant effects. However, potential pro-tumorigenic impacts require careful consideration for therapeutic applications.
Area of Science:
- Cellular Biology
- Molecular Medicine
- Wound Healing Research
Background:
- The nuclear factor-erythroid 2-related factor 2 (NRF2) pathway is crucial for cellular stress response and antioxidant defense.
- NRF2 activators are explored for disease prevention and therapy due to their antioxidant properties.
- Chronic wounds represent a significant health and economic challenge, necessitating novel treatment strategies.
Purpose of the Study:
- To review the current evidence on the role of NRF2 pathway activation in wound healing.
- To evaluate the therapeutic potential of NRF2 activators for chronic wound treatment.
- To discuss the dual role of NRF2, including its potential pro-tumorigenic effects, in the context of wound healing.
Main Methods:
- Comprehensive literature review of existing studies on NRF2 and wound healing.
- Analysis of data from gain- and loss-of-function animal models investigating NRF2's role.
- Correlation of animal model findings with human observations and clinical data.
Main Results:
- Evidence suggests NRF2 pathway activation significantly impacts wound healing processes.
- NRF2 activation demonstrates potential benefits for treating chronic wounds.
- Conversely, studies indicate that NRF2 activation may also promote tumor growth.
Conclusions:
- NRF2 pathway modulation presents a promising avenue for chronic wound management.
- Therapeutic strategies targeting NRF2 must carefully balance its beneficial effects on healing against potential oncogenic risks.
- Further research integrating animal and human data is essential to optimize NRF2-based wound therapies.
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