title: Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.
abstract: The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlierin vitro. The Transforming Growth Factor beta (TGFb) produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.
authors.affiliation: Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Demyanenko
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.|Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Ekaterina N
authors.initials: EN
authors.lastname: Popova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.|Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Vlada V
authors.initials: VV
authors.lastname: Zakharova
authors.affiliation: Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Olga P
authors.initials: OP
authors.lastname: Ilyinskaya
authors.affiliation: Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Tamara V
authors.initials: TV
authors.lastname: Vasilieva
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Valeria P
authors.initials: VP
authors.lastname: Romashchenko
authors.affiliation: Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Artem V
authors.initials: AV
authors.lastname: Fedorov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.|Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Vasily N
authors.initials: VN
authors.lastname: Manskikh
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.|Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Skulachev
authors.affiliation: Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.|Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Roman A
authors.initials: RA
authors.lastname: Zinovkin
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.|Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Pletjushkina
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.|Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.|Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Skulachev
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.|Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Boris V
authors.initials: BV
authors.lastname: Chernyak
mesh_terms: D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008928:Mitochondria / Q000187:drug effects*; D058628:Myofibroblasts / Q000378:metabolism; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000293:injuries; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D015820:Cadherins; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D010971:Plastoquinone
keywords: mitochondria-targeted antioxidant; mitochondrial reactive oxygen species; wound healing