Folic Acid Promotes Wound Healing in Diabetic Mice by Suppression of Oxidative Stress

Zhao, Mingqiu; Zhou, Jun; Chen, Yuan-Hua; Li, Yuan; Yuan, Man-man; Zhang, Xinqiong; Huang, Yan; Yu, Huan

doi:10.3177/jnsv.64.26

Cited by 20 publications

(26 citation statements)

References 29 publications

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“…In this study, we established a type 1 diabetes model with mouse by injecting STZ intraperitoneally. Although type 2 diabetes accounts for about 90% of total diabetic patients, type 1 diabetes animal models are more widely used in the study of diabetic wounds, because of its uncomplicated preparation, high modeling rate, and consistent abnormal glucose metabolism process with type 2 diabetes [28][29]. Our research results con rmed that KLX accelerated the healing speed of diabetic wounds.…”

Section: Discussionsupporting

confidence: 60%

Kanglexin promotes diabetic wound healing through activating FGFR/ERK1/2 signaling pathway mediated angiogenesis.

Zhao¹,

Wang²,

Yang³

et al. 2020

Preprint

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Background: Diabetic wounds (DWs), especially leg or foot ulcers, are common diabetic complications, accounting for about 20% of diabetic patients. At present, there is still lack of effective measures to treat DWs in clinical practice. Kanglexin (KLX) is an anthraquinone compound with vasoprotective effect. This study will explore the therapeutic effects of KLX on DWs and the underlying mechanisms.Method: KM mice were injected with streptozocin (180 mg/kg) intraperitoneally to establish animal model of Type 1 Diabetes. The full-thickness skin wounds with the diameter of 5 mm were prepared on the back of diabetic mice with a skin punch. KLX is dissolved in sterile injection oil and applied to the wound once a day for 14 consecutive days. The wounds were photographed every day and the wound size was analyzed by Image Pro Plus software. On the 3rd, 7th, 11th day after KLX administration, skin tissues with a diameter of 1cm around the wound were fixed in paraformaldehyde and subjected to HE, Masson and immunohistochemical staining. Collagen deposition were evaluated by hydroxyproline kit. Angiogenesis of wound skin was evaluated by recording the formation of new blood vessels on its subsurface. In vitro study, human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs, 100 μg/mL) to establish the cell model of DWs. The proliferation, migration and tubular structure formation of HUVECs were measured by MTT, scratch and tubule formation experiments, respectively. Phosphorylation of ERK1/2 was detected by Western blot analysis.ResultsFirstly, in-vivo study showed that KLX significantly accelerated the closure of diabetic wounds through promoting granulation tissue formation, collagen synthesis and angiogenesis. Secondly, in vitro study results further confirmed that KLX promoted the proliferation, migration and tubular structure formation of HUVECs. Besides, KLX significantly up-regulated phospho-ERK1/2 both in diabetic wounds and AGEs-treated HUVECs. Thirdly, molecular docking simulation results indicated that there were multiple hydrogen bonds between KLX and FGFR amino acid residues, and FGFR inhibitor PD173074 significantly reversed KLX’s promotion of ERK1/2 phosphorylation and angiogenesis. Conclusions:KLX promotes angiogenesis and accelerates the healing of diabetic wounds by activating FGFR and ERK1/2 signaling pathway.

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Section: Discussionsupporting

confidence: 60%

Kanglexin promotes diabetic wound healing through activating FGFR/ERK1/2 signaling pathway mediated angiogenesis.

Zhao¹,

Wang²,

Yang³

et al. 2020

Preprint

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“…VEGF accelerates healing by recruiting endothelial progenitor cells to the skin of mice that are hyperglycemic, due to a genetic deletion in the leptin receptor (Lepr db/db ) [449]. Intriguingly, diabetic mice that received folic acid orally showed increased levels of hydroxyproline, a major component of collagen, and enhanced re-epithelialization, suggesting that folic acid increases collagen turnover and wound closure [450]. Hydrogen sulfide has also been shown to exert therapeutic effects on wound healing in Lep ob mice, by attenuating inflammation at the injury site [451].…”

Section: Skin Immune Responses In Wound Healingmentioning

confidence: 99%

The Dynamics of the Skin’s Immune System

Nguyen

Soulika

2019

IJMS

465

339

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The skin is a complex organ that has devised numerous strategies, such as physical, chemical, and microbiological barriers, to protect the host from external insults. In addition, the skin contains an intricate network of immune cells resident to the tissue, crucial for host defense as well as tissue homeostasis. In the event of an insult, the skin-resident immune cells are crucial not only for prevention of infection but also for tissue reconstruction. Deregulation of immune responses often leads to impaired healing and poor tissue restoration and function. In this review, we will discuss the defensive components of the skin and focus on the function of skin-resident immune cells in homeostasis and their role in wound healing.

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“…A). Hydroxyproline levels are regarded as an indicator of tissue collagen deposition . STZ decreased tissue hydroxyproline levels, whereas TY001 and WP increased tissue hydroxyproline levels (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…STZ‐induced diabetic model was established by intraperitoneal injection of STZ (50 mg kg −1 in citrate buffer) or 0.1 mmol L –1 citrate buffer, pH 4.5, 10 mL kg −1 ), daily for consecutive 5 days. One week after the last STZ injection, tail blood was taken for blood glucose determination, and the criteria for diabetes was blood glucose >250 mg dL −1 …”

Section: Methodsmentioning

confidence: 99%

The wound healing effects of the Tilapia collagen peptide mixture TY001 in streptozotocin diabetic mice

Xiong

Liang

Xu³

et al. 2020

J Sci Food Agric

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BACKGROUND The Tilapia collagen peptides mixture TY001 is effective in promoting wound healing in acetic acid‐induced skin lesions in zebrafish and in protecting against lipopolysaccharide‐induced inflammation and disruption of glucose metabolism in mice. The present study aimed to further examine the wound healing effects of TY001 in streptozotocin‐induced diabetic mice. METHODS Full‐thickness skin excision wounds were created with 8‐mm biopsy punches and TY001 was administered via drinking water (15, 30 and 45 g L−1 in emulsion) for 15 days. RESULTS Wound healing was delayed in diabetic mice but was promoted by TY001 after 5, 10 or 15 days of treatment. Collagen deposition and tissue hydroxyproline contents were increased by TY001. The expressions of insulin growth factor‐1, basic fibroblast growth factor, platelet‐derived growth factor, transforming growth facts β1, vascular endothelial growth factor and epidermal growth factor were increased by TY001, as indicated by immunobiochemistry and a quantitative polymerase chain reaction. Diabetes‐associated serum pro‐inflammatory cytokines interleukin (IL)‐1β and IL‐8 were decreased, whereas anti‐inflammatory IL‐10 and nitric oxide were increased by TY001, along with increased tissue antioxidant superoxide dismutase and catalase activities. Diabetes‐reduced serum protein levels were also recovered by TY001 CONCLUSION Taken together, Tilapia collagen peptide mixture TY001 was effective with respect to enhancing diabetes‐associated wound healing delay, probably via increasing growth factors and collagen deposition in the wound, attenuating diabetes‐induced prolonged inflammation, increasing tissue antioxidants and providing nutritional support in diabetic mice. © 2019 Society of Chemical Industry

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Folic Acid Promotes Wound Healing in Diabetic Mice by Suppression of Oxidative Stress

Cited by 20 publications

References 29 publications

Kanglexin promotes diabetic wound healing through activating FGFR/ERK1/2 signaling pathway mediated angiogenesis.

Kanglexin promotes diabetic wound healing through activating FGFR/ERK1/2 signaling pathway mediated angiogenesis.

The Dynamics of the Skin’s Immune System

The wound healing effects of the Tilapia collagen peptide mixture TY001 in streptozotocin diabetic mice

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