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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

Effect of SkQ1 on the cellular composition of the wound(a) Representative micrographs of the H&E stained transverse sections at the edge of the wounds at 7d and 13d. (b) Edges of the wounds at 7d and 13d stained with antibodies against the macrophage marker F4/80. (c) Total cellular content, (d) infiltration of neutrophils and (e) macrophages (F4/80 positive cells) in granulation tissue at 7d and 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 4: Effect of SkQ1 on the cellular composition of the wound(a) Representative micrographs of the H&E stained transverse sections at the edge of the wounds at 7d and 13d. (b) Edges of the wounds at 7d and 13d stained with antibodies against the macrophage marker F4/80. (c) Total cellular content, (d) infiltration of neutrophils and (e) macrophages (F4/80 positive cells) in granulation tissue at 7d and 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: Histological analysis revealed that old mice had significantly higher neutrophil content compared to the young animals at 7 day and even at 13 day after wounding. This phenomenon was described earlier for aged animals and humans [38, 39]. Treatment with SkQ1 strongly decreased the neutrophil infiltration in old mice (Fig. 4a, d). In parallel with increased neutrophil content, delayed infiltration of macrophages was observed in old mice while SkQ1 treatment accelerated this process (Fig. 4b, e). SkQ1 decreased macrophage content at 13 day to the level similar to that in young mice. These observations indicated that SkQ1 accelerated resolution of inflammatory phase.


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)

Effect of SkQ1 on the cellular composition of the wound(a) Representative micrographs of the H&E stained transverse sections at the edge of the wounds at 7d and 13d. (b) Edges of the wounds at 7d and 13d stained with antibodies against the macrophage marker F4/80. (c) Total cellular content, (d) infiltration of neutrophils and (e) macrophages (F4/80 positive cells) in granulation tissue at 7d and 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 4: Effect of SkQ1 on the cellular composition of the wound(a) Representative micrographs of the H&E stained transverse sections at the edge of the wounds at 7d and 13d. (b) Edges of the wounds at 7d and 13d stained with antibodies against the macrophage marker F4/80. (c) Total cellular content, (d) infiltration of neutrophils and (e) macrophages (F4/80 positive cells) in granulation tissue at 7d and 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: Histological analysis revealed that old mice had significantly higher neutrophil content compared to the young animals at 7 day and even at 13 day after wounding. This phenomenon was described earlier for aged animals and humans [38, 39]. Treatment with SkQ1 strongly decreased the neutrophil infiltration in old mice (Fig. 4a, d). In parallel with increased neutrophil content, delayed infiltration of macrophages was observed in old mice while SkQ1 treatment accelerated this process (Fig. 4b, e). SkQ1 decreased macrophage content at 13 day to the level similar to that in young mice. These observations indicated that SkQ1 accelerated resolution of inflammatory phase.

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