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Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing

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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 ρ0 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.

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Acknowledgments

Studies presented in this manuscript were fully supported by the Dermatology Foundation research grant to Jana Jandova.

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Authors and Affiliations

  1. University of Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA

    Jaroslav Janda, Valentine Nfonsam, Fernanda Calienes, James E. Sligh & Jana Jandova

  2. Department of Surgery, Division of Surgical Oncology, University of Arizona, 1501 N Campbell Avenue, Tucson, AZ, 85724, USA

    Valentine Nfonsam & Jana Jandova

  3. Department of Medicine, Division of Dermatology, University of Arizona, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA

    James E. Sligh & Jana Jandova

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  1. Jaroslav Janda
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  2. Valentine Nfonsam
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  3. Fernanda Calienes
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  4. James E. Sligh
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  5. Jana Jandova
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Correspondence to Jana Jandova.

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Janda, J., Nfonsam, V., Calienes, F. et al. Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing. Arch Dermatol Res 308, 239–248 (2016). https://doi.org/10.1007/s00403-016-1628-9

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  • DOI: https://doi.org/10.1007/s00403-016-1628-9

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