title: Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.
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.
authors.affiliation: University of Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Janda
authors.affiliation: University of Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA.|Department of Surgery, Division of Surgical Oncology, University of Arizona, 1501 N Campbell Avenue, Tucson, AZ, 85724, USA.
authors.forename: Valentine
authors.initials: V
authors.lastname: Nfonsam
authors.affiliation: University of Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Calienes
authors.affiliation: University of Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA.|Department of Medicine, Division of Dermatology, University of Arizona, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Sligh
authors.affiliation: University of Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA. jjandova@email.arizona.edu.|Department of Surgery, Division of Surgical Oncology, University of Arizona, 1501 N Campbell Avenue, Tucson, AZ, 85724, USA. jjandova@email.arizona.edu.|Department of Medicine, Division of Dermatology, University of Arizona, 1515 N Campbell Avenue, Tucson, AZ, 85724, USA. jjandova@email.arizona.edu.
authors.forename: Jana
authors.initials: J
authors.lastname: Jandova
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D012879:Skin Physiological Phenomena; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species
keywords: Antioxidants; Gap closure; Gene expression; Mitochondria; Reactive oxygen species