Archives of Dermatological Research

, Volume 308, Issue 4, pp 239–248 | Cite as

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

  • Jaroslav Janda
  • Valentine Nfonsam
  • Fernanda Calienes
  • James E. Sligh
  • Jana Jandova
Original Paper

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.

Keywords

Mitochondria Reactive oxygen species Antioxidants Gene expression Gap closure 

Supplementary material

403_2016_1628_MOESM1_ESM.pdf (430 kb)
Supplementary material 1 (PDF 429 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jaroslav Janda
    • 1
  • Valentine Nfonsam
    • 1
    • 2
  • Fernanda Calienes
    • 1
  • James E. Sligh
    • 1
    • 3
  • Jana Jandova
    • 1
    • 2
    • 3
  1. 1.University of Arizona Cancer CenterTucsonUSA
  2. 2.Department of Surgery, Division of Surgical OncologyUniversity of ArizonaTucsonUSA
  3. 3.Department of Medicine, Division of DermatologyUniversity of ArizonaTucsonUSA

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