Growth Factors, Reactive Oxygen Species, and Metformin—Promoters of the Wound Healing Process in Burns?

Miricescu, Daniela; Bădoiu, Silviu Constantin; Stănescu-Spînu, Iulia-Ioana; Totan, Alexandra Ripszky; Ştefani, Constantin; Greabu, Maria

doi:10.3390/ijms22179512

Cited by 30 publications

(22 citation statements)

References 187 publications

(233 reference statements)

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“…Moreover, metformin treatment improved the blood perfusion of the mechanically stretched skin, with subsequent histologic evaluation and quantitative assessment of CD31+ blood vessels confirming the improved angiogenesis in the metformin-treated group. Previous studies report that metformin promotes tissue repair directly or indirectly ( 14 ), mainly by improving the angiogenesis of wounds ( 10 , 19 , 20 ). Because mechanically stretched skin experiences similar stress and relaxation activities to that in injury- and repair-related mechanical stretching processes ( 18 ), the proangiogenic effect of metformin during wound healing is likely replicated in mechanically stretched skin.…”

Section: Discussionmentioning

confidence: 99%

“…Growing evidence shows that topical application of metformin might favor tissue regeneration and wound repair, which partially correlates with promoting angiogenesis and activating HFBSCs ( 9 , 10 ). Other studies suggest that metformin accelerates wound healing by increasing dermal collagen deposition and re-epithelialization ( 10 – 14 ). Coincidentally, the mechanical stretching process involves both cyclic damage and repair.…”

Section: Introductionmentioning

confidence: 99%

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Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

et al. 2022

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BackgroundSkin expansion by mechanical stretch is an essential and widely used treatment for tissue defects in plastic and reconstructive surgery; however, the regenerative capacity of mechanically stretched skin limits clinical treatment results. Here, we propose a strategy to enhance the regenerative ability of mechanically stretched skin by topical application of metformin.MethodsWe established a mechanically stretched scalp model in male rats (n = 20), followed by their random division into two groups: metformin-treated (n = 10) and control (n = 10) groups. We measured skin thickness, collagen volume fraction, cell proliferation, and angiogenesis to analyze the effects of topical metformin on mechanically stretched skin, and immunofluorescence staining was performed to determine the contents of epidermal stem cells and hair follicle bulge stem cells in mechanically stretched skin. Western blot was performed to detect the protein expression of skin-derived stem cell markers.ResultsCompared with the control group, metformin treatment was beneficial to mechanical stretch-induced skin regeneration by increasing the thicknesses of epidermis (57.27 ± 10.24 vs. 31.07 ± 9.06 μm, p < 0.01) and dermis (620.2 ± 86.17 vs. 402.1 ± 22.46 μm, p < 0.01), number of blood vessels (38.30 ± 6.90 vs. 17.00 ± 3.10, p < 0.01), dermal collagen volume fraction (60.48 ± 4.47% vs. 41.28 ± 4.14%, p < 0.01), and number of PCNA+, Aurora B+, and pH3+ cells. Additionally, we observed significant elevations in the number of proliferating hair follicle bulge stem cells [cytokeratin (CK)15+/proliferating cell nuclear antigen (PCNA)+] (193.40 ± 35.31 vs. 98.25 ± 23.47, p < 0.01) and epidermal stem cells (CK14+/PCNA+) (83.00 ± 2.38 vs. 36.38 ± 8.96, p < 0.01) in the metformin-treated group, and western blot results confirmed significant increases in CK14 and CK15 expression following metformin treatment.ConclusionTopical application of metformin enhanced the regenerative capacity of mechanically stretched skin, with the underlying mechanism possibly attributed to improvements in the proliferative activity of skin-derived stem cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

et al. 2022

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“…The creation of granulation tissue and epithelialization are other important phenomena in this healing period. In the proliferation phase of healing, fibroblasts are the most important cells [ 22 , 23 ]. For fibroblasts to migrate in the extracellular matrix, they must first recognize and interact with particular matrix components.…”

Section: The Process Of Wound Healingmentioning

confidence: 99%

A Comprehensive Review of Natural Compounds for Wound Healing: Targeting Bioactivity Perspective

Trinh

Long

Anh

et al. 2022

IJMS

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Wound healing is a recovering process of damaged tissues by replacing dysfunctional injured cellular structures. Natural compounds for wound treatment have been widely used for centuries. Numerous published works provided reviews of natural compounds for wound healing applications, which separated the approaches based on different categories such as characteristics, bioactivities, and modes of action. However, current studies provide reviews of natural compounds that originated from only plants or animals. In this work, we provide a comprehensive review of natural compounds sourced from both plants and animals that target the different bioactivities of healing to promote wound resolution. The compounds were classified into four main groups (i.e., anti-inflammation, anti-oxidant, anti-bacterial, and collagen promotion), mostly studied in current literature from 1992 to 2022. Those compounds are listed in tables for readers to search for their origin, bioactivity, and targeting phases in wound healing. We also reviewed the trend in using natural compounds for wound healing.

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“…Growth factors contribute to cell proliferation and differentiation in embryogenesis [132]. The signaling of the epidermal growth factor receptor (EGFR) shows a redoxregulated linkage to tyrosine kinase signaling, which is redox-sensitive [133].…”

Section: Growth Factors and Redox Modulationmentioning

confidence: 99%

Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis

Chen

Tjong

Yang

et al. 2022

IJMS

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Normal embryogenesis requires complex regulation and precision, which depends on multiple mechanistic details. Defective embryogenesis can occur by various mechanisms. Maintaining redox homeostasis is of importance during embryogenesis. NADPH, as produced from the action of glucose-6-phosphate dehydrogenase (G6PD), has an important role in redox homeostasis, serving as a cofactor for glutathione reductase in the recycling of glutathione from oxidized glutathione and for NADPH oxidases and nitric oxide synthases in the generation of reactive oxygen (ROS) and nitrogen species (RNS). Oxidative stress differentially influences cell fate and embryogenesis. While low levels of stress (eustress) by ROS and RNS promote cell growth and differentiation, supra-physiological concentrations of ROS and RNS can lead to cell demise and embryonic lethality. G6PD-deficient cells and organisms have been used as models in embryogenesis for determining the role of redox signaling in regulating cell proliferation, differentiation and migration. Embryogenesis is also modulated by anti-oxidant enzymes, transcription factors, microRNAs, growth factors and signaling pathways, which are dependent on redox regulation. Crosstalk among transcription factors, microRNAs and redox signaling is essential for embryogenesis.

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Growth Factors, Reactive Oxygen Species, and Metformin—Promoters of the Wound Healing Process in Burns?

Cited by 30 publications

References 187 publications

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells

A Comprehensive Review of Natural Compounds for Wound Healing: Targeting Bioactivity Perspective

Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis

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