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Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.

Demyanenko IA, Popova EN, Zakharova VV, Ilyinskaya OP, Vasilieva TV, Romashchenko VP, Fedorov AV, Manskikh VN, Skulachev MV, Zinovkin RA, Pletjushkina OY, Skulachev VP, Chernyak BV - Aging (Albany NY) (2015)

Bottom Line: 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.Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.

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.

No MeSH data available.


Related in: MedlinePlus

SkQ1 promotes granulation tissue formation and epithelization of old mice wound, but does not cause scar hypertrophyH&E staining of transverse sections of the wounds of old mice at 7d (a) and at 13d (d); area of granulation tissue or scar is shown by the black dotted line. (b) Granulation tissue formation, and (c) epithelization of the wounds at 7d; (e) scar formation at 13d. Data are presented as mean ± SD; *P < 0.05 for SkQ1-treated versus control; ‡P < 0.05 for the untreated young versus old mice.
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Figure 2: SkQ1 promotes granulation tissue formation and epithelization of old mice wound, but does not cause scar hypertrophyH&E staining of transverse sections of the wounds of old mice at 7d (a) and at 13d (d); area of granulation tissue or scar is shown by the black dotted line. (b) Granulation tissue formation, and (c) epithelization of the wounds at 7d; (e) scar formation at 13d. Data are presented as mean ± SD; *P < 0.05 for SkQ1-treated versus control; ‡P < 0.05 for the untreated young versus old mice.

Mentions: SkQ1 stimulated spreading of granulation tissue over the wounded area accelerating collagen fibers formation and maturation in old mice (Figs. 2, 3). Granulation tissue of SkQ1-treated mice contained increased amount of fibroblast-like cells expressing smooth muscle α-actin (α-SMA), (Fig. 3). Compared to fibroblasts, these cells referred to myofibroblasts produce more collagen, other extracellular matrix proteins and growth factors involved in granulation tissue formation and angiogenesis in wounds [35]. This finding was in perfect agreement with our earlier observations on SkQ1-induced myofibroblast differentiation of human subcutaneous fibroblasts in vitro [31].


Mitochondria-targeted antioxidant SkQ1 improves impaired dermal wound healing in old mice.

Demyanenko IA, Popova EN, Zakharova VV, Ilyinskaya OP, Vasilieva TV, Romashchenko VP, Fedorov AV, Manskikh VN, Skulachev MV, Zinovkin RA, Pletjushkina OY, Skulachev VP, Chernyak BV - Aging (Albany NY) (2015)

SkQ1 promotes granulation tissue formation and epithelization of old mice wound, but does not cause scar hypertrophyH&E staining of transverse sections of the wounds of old mice at 7d (a) and at 13d (d); area of granulation tissue or scar is shown by the black dotted line. (b) Granulation tissue formation, and (c) epithelization of the wounds at 7d; (e) scar formation at 13d. Data are presented as mean ± SD; *P < 0.05 for SkQ1-treated versus control; ‡P < 0.05 for the untreated young versus old mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543037&req=5

Figure 2: SkQ1 promotes granulation tissue formation and epithelization of old mice wound, but does not cause scar hypertrophyH&E staining of transverse sections of the wounds of old mice at 7d (a) and at 13d (d); area of granulation tissue or scar is shown by the black dotted line. (b) Granulation tissue formation, and (c) epithelization of the wounds at 7d; (e) scar formation at 13d. Data are presented as mean ± SD; *P < 0.05 for SkQ1-treated versus control; ‡P < 0.05 for the untreated young versus old mice.
Mentions: SkQ1 stimulated spreading of granulation tissue over the wounded area accelerating collagen fibers formation and maturation in old mice (Figs. 2, 3). Granulation tissue of SkQ1-treated mice contained increased amount of fibroblast-like cells expressing smooth muscle α-actin (α-SMA), (Fig. 3). Compared to fibroblasts, these cells referred to myofibroblasts produce more collagen, other extracellular matrix proteins and growth factors involved in granulation tissue formation and angiogenesis in wounds [35]. This finding was in perfect agreement with our earlier observations on SkQ1-induced myofibroblast differentiation of human subcutaneous fibroblasts in vitro [31].

Bottom Line: 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.Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.

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.

No MeSH data available.


Related in: MedlinePlus