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Updated: Mar 25, 2026
Murine Excisional Wound Healing Model and Histological Morphometric Wound Analysis
Published on: August 21, 2020
Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing
Jaroslav Janda1, Valentine Nfonsam1,2, Fernanda Calienes1
1University of Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA.
Abstract:
Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.
Insights
Mitochondrial reactive oxygen species (ROS) regulate fibroblast gene expression crucial for wound healing. Modulating mitochondrial ROS with antioxidants enhances wound closure, offering a redox-based strategy for treating non-healing wounds.
Area of Science:
- Cell Biology
- Biochemistry
- Genetics
Background:
- Mitochondria are primary sources of reactive oxygen species (ROS) in fibroblasts, playing a key role in regulating wound healing.
- The precise mechanisms controlling mitochondrial ROS generation and their impact on nuclear gene expression during tissue repair are not fully understood.
- ROS are implicated in all phases of tissue repair, highlighting the need to understand their regulatory systems in fibroblasts.
Purpose of the Study:
- To elucidate the molecular mechanisms by which mitochondrial ROS levels influence wound repair processes.
- To investigate the functional consequences of altered ROS levels on wound healing in a controlled cellular model.
- To explore the relationship between mitochondrial ROS, nuclear gene expression, and fibroblast behavior in wound healing.
Main Methods:
- Utilized a cybrid model system with variations in mitochondrial DNA (mtDNA) to study ROS effects in a consistent nuclear background (ρ(0) fibroblasts).
- Modulated mitochondrial ROS levels using antioxidants to assess their impact on in vitro wound closure.
- Employed real-time PCR arrays to analyze the expression of key nuclear-encoded genes involved in wound healing and oxidative stress in response to varying ROS levels.
Main Results:
- Mitochondrial ROS levels were found to significantly affect the expression of specific nuclear genes central to wound healing and oxidative stress.
- Antioxidant-mediated modulation of mitochondrial ROS demonstrated a positive effect on the rate of in vitro wound closure.
- The study identified a link between specific mtDNA variants, ROS production, and downstream effects on nuclear gene regulation.
Conclusions:
- Regulation of mitochondrial ROS in fibroblasts is a critical factor influencing wound healing responses.
- Targeting mitochondrial ROS production presents a potential natural redox-based therapeutic strategy for managing non-healing wounds.
- Understanding the interplay between mitochondrial function and nuclear gene expression is key to developing novel wound healing treatments.
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