scholarly journals Interleukin 6 Function in the Skin and Isolated Keratinocytes Is Modulated by Hyperglycemia

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Eric G. Lee ◽  
Lerin R. Luckett-Chastain ◽  
Kaitlin N. Calhoun ◽  
Benjamin Frempah ◽  
Anja Bastian ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Interleukin 6 ◽  
Wound Closure ◽  
Cultured Cells ◽  
Health Care Cost ◽  
Epidermal Keratinocytes ◽  
Type I ◽  
Primary Mouse ◽  
Time Point

Diabetes currently affects over twenty-five million Americans. Annual health care cost of diabetes exceeds $254 billion and is associated with a distinct set of diabetic complications that include delayed wound healing and diabetic ulcers. Interleukin 6 (IL-6) plays an important role in wound healing and is known to be elevated in the serum of both type I and type II diabetes patients. This study assesses the expression and function of IL-6 in the hyperglycemic epidermis and keratinocyte culture. Streptozotocin-treated mice were wounded six weeks after induction of hyperglycemia. Wound closure, protein, and mRNA expression were assessed up to 13 days of postwounding. Wound closure was delayed 4-5 days in hyperglycemic animals. Hyperglycemic wounds displayed greater IL-6 and IL-6Rα protein expression at 1, 7, and 10 days of postwounding compared to euglycemic control. However, IL-6Rα mRNA expression was reduced at all time points beyond day 1, while IL-6 mRNA expression did not significantly differ at any time point. SOCS3 mRNA expression was higher in the hyperglycemic skin at every time point. Imaging of fluorescent immunohistology also revealed significantly lower expression of SOCS3, but higher nuclear pSTAT3 in the epidermis of the hyperglycemic skin. Primary mouse keratinocytes cultured in high glucose for 7 days displayed 2-fold higher IL-6Rα mRNA and higher rmIL-6-induced nuclear pSTAT3, but lower SOCS3 basal levels compared to normal glucose-cultured cells. Thus, it appears that delayed diabetic skin wound healing is associated with increased induction and expression of IL-6 and its receptor, but its function in epidermal keratinocytes may be impaired.

scholarly journals 12-hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor

2014 ◽  
Vol 211 (6) ◽  
pp. 1063-1078 ◽  
Author(s):  
Min Liu ◽  
Kazuko Saeki ◽  
Takehiko Matsunobu ◽  
Toshiaki Okuno ◽  
Tomoaki Koga ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Cultured Cells ◽  
Leukotriene B4 ◽  
Epidermal Keratinocytes ◽  
Skin Wound Healing ◽  
Wound Fluid ◽  
Deficient Mice

Leukotriene B4 (LTB4) receptor type 2 (BLT2) is a G protein–coupled receptor (GPCR) for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4. Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive. As mouse BLT2 is highly expressed in epidermal keratinocytes, we investigated the role of the 12-HHT/BLT2 axis in skin wound healing processes. 12-HHT accumulated in the wound fluid in mice, and BLT2-deficient mice exhibited impaired re-epithelialization and delayed wound closure after skin punching. Aspirin administration reduced 12-HHT production and resulted in delayed wound closure in wild-type mice, which was abrogated in BLT2-deficient mice. In vitro scratch assay using primary keratinocytes and a keratinocyte cell line also showed that the 12-HHT/BLT2 axis accelerated wound closure through the production of tumor necrosis factor α (TNF) and matrix metalloproteinases (MMPs). A synthetic BLT2 agonist accelerated wound closure in cultured cells as well as in C57BL/6J and diabetic mice. These results identify a novel mechanism underlying the action of the 12-HHT/BLT2 axis in epidermal keratinocytes and accordingly suggest the use of BLT2 agonists as therapeutic agents to accelerate wound healing, particularly for intractable wounds, such as diabetic ulcers.

scholarly journals Investigating potential wound healing properties of polysaccharides extracted from Grewia mollis Juss. and Hoheria populnea A. Cunn. (Malvaceae)

2020 ◽  
Author(s):  
N Pearman ◽  
SR Moxon ◽  
Susan Carnachan ◽  
ME Cooke ◽  
EI Nep ◽  
...  
Keyword(s):  
Wound Healing ◽  
Traditional Medicine ◽  
Quantitative Pcr ◽  
Wound Closure ◽  
Type I Collagen ◽  
Type I ◽  
Closure Rate ◽  
Scratch Assay ◽  
Grewia Gum ◽  
Positive Effect

© 2019 Elsevier Ltd The Malvaceae family is a group of flowering plants that include approximately 244 genera, and 4225 species. Grewia mollis, and Hoheria populnea (lacebark), are examples of the Malvaceae family that are used in traditional medicine. For this study polysaccharide samples were extracted from the inner bark of Grewia mollis (unmodified (GG) and destarched grewia gum (GGDS)) and from the leaves of Hoheria populnea (lacebark polysaccharide (LB)). Wound healing properties of grewia gum and lacebark polysaccharides were investigated using 3T3 fibroblast cells cultured in supplemented DMEM. Deposition of collagen using van Gieson's stain, expression of the COL1A1 gene which encodes type I collagen using quantitative PCR, and chemotaxis using a scratch plate assay were analysed following treatment of cells with the test polysaccharides. Quantitative PCR results indicated that all three polysaccharides increased the levels of COL1A1 mRNA, with GG showing the greatest fold change. Histological staining also indicated that the fibroblasts treated with GG deposited more collagen than control cells. Additionally, scratch assay data indicated that simulated cell ‘wounds’ treated with each polysaccharide showed increased wound closure rate over a 36 h period post treatment, with GG exhibiting the greatest effect on wound closure. Analysis of the Malvaceae derived polysaccharides indicates that they could have a positive effect on mechanisms that are integral to wound healing, potentially providing greater scientific understanding behind their use in traditional medicine.

scholarly journals Specific PKC βII inhibitor: one stone two birds in the treatment of diabetic foot ulcers

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Sushant Kumar Das ◽  
Yi Feng Yuan ◽  
Mao Quan Li
Keyword(s):  
Wound Healing ◽  
Protein Kinase ◽  
Peripheral Blood ◽  
Wound Closure ◽  
Type I Diabetes ◽  
Healing Process ◽  
Wound Healing Process ◽  
Peripheral Blood Flow ◽  
Type I ◽  
Diabetic Mice

To explore whether or not inhibition of protein kinase C βII (PKC βII) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Streptozotocin (STZ, 60 mg/kg/day for 5 days, i.p.) was injected to induce type I diabetes in male ICR mice. Mice were treated with ruboxistaurin (30 mg/kg/day, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31-stained capillaries. Peripheral blood flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs). NETosis assay and wound tissue immunofluorescence imaging were done to evaluate the percentage of neutrophils undergoing NETosis. Furthermore, the expression of PKC βII, protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and histone citrullation (H3Cit) were determined in the wound by Western blot analysis. Ruboxistaurin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in ruboxistaurin-treated diabetic mice. Moreover, ruboxistaurin treatment significantly decreases the percentages of H3Cit+ cells in both peripheral blood and wound areas. This prevented excess activated neutrophils forming an extracellular trap (NETs) formation. The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment. The expressions of PKC βII and H3Cit+, on the other hand, decreased with ruboxistaurin treatment. The results of the present study suggest that ruboxistaurin by inhibiting PKC βII activation, reverses EPCs dysfunction as well as prevents exaggerated NETs formation in a diabetic mouse model; thereby accelerating the wound healing process.

Soluble and insoluble fibronectin increases alveolar epithelial wound healing in vitro

1996 ◽  
Vol 271 (5) ◽  
pp. L844-L853 ◽  
Author(s):  
C. Garat ◽  
F. Kheradmand ◽  
K. H. Albertine ◽  
H. G. Folkesson ◽  
M. A. Matthay
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Type Iv Collagen ◽  
Type I ◽  
Serum Free Medium ◽  
Free Medium ◽  
Alveolar Epithelial ◽  
Type Iv ◽  
Epithelial Wound Healing

Adhesive interactions between cells and extracellular matrix proteins are important in cell attachment, migration, and proliferation. The present work defines the role of fibronectin (soluble and insoluble) compared with type I and type IV collagen on in vitro alveolar epithelial wound healing. Repeated video microscopy experiments demonstrated that the half-time of wound closure was decreased in the presence of soluble fibronectin (6.6 +/- 2.1 vs. 17.4 +/- 0.8 h in serum-free medium, P < 0.05). Video microscopy, electron microscopy, and vinculin distribution demonstrated the contribution of two main events during the repair process: the migration of epithelial cell sheets and the spreading of the cells. During the wound healing, the internuclear distance between two adjacent cells at the migrating edge of the wound was significantly increased 10 h after wounding in the presence of soluble fibronectin (67 +/- 3.0 vs. 45 +/- 1.5 microns in serum-free medium, P < 0.05), indicating that cell spreading is involved as part of the mechanism for wound closure. Compared with type I and type IV collagen, insoluble fibronectin was the most potent stimulus for alveolar type II cell motility and wound healing in the absence of other serum factors. These results demonstrate that alveolar epithelial wound healing can be modulated in vitro by the composition of the extracellular matrix, an effect that may be mediated by changes in cell shape.

scholarly journals Ferulic Acid Induces Keratin 6α via Inhibition of Nuclear β-Catenin Accumulation and Activation of Nrf2 in Wound-Induced Inflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 459
Author(s):  
Kang-Hoon Kim ◽  
Ji Hoon Jung ◽  
Won-Seok Chung ◽  
Chang-Hun Lee ◽  
Hyeung-Jin Jang
Keyword(s):  
Wound Healing ◽  
Ferulic Acid ◽  
Wound Closure ◽  
Secondary Infection ◽  
Bioactive Compound ◽  
Explant Culture ◽  
Negative Regulator ◽  
Epidermal Keratinocytes ◽  
Related Factor ◽  
Human Epidermal Keratinocytes

Injured tissue triggers complex interactions through biological process associated with keratins. Rapid recovery is most important for protection against secondary infection and inflammatory pain. For rapid wound healing with minimal pain and side effects, shilajit has been used as an ayurvedic medicine. However, the mechanisms of rapid wound closure are unknown. Here, we found that shilajit induced wound closure in an acute wound model and induced migration in skin explant cultures through evaluation of transcriptomics via microarray testing. In addition, ferulic acid (FA), as a bioactive compound, induced migration via modulation of keratin 6α (K6α) and inhibition of β-catenin in primary keratinocytes of skin explant culture and injured full-thickness skin, because accumulation of β-catenin into the nucleus acts as a negative regulator and disturbs migration in human epidermal keratinocytes. Furthermore, FA alleviated wound-induced inflammation via activation of nuclear factor erythroid-2-related factor 2 (Nrf2) at the wound edge. These findings show that FA is a novel therapeutic agent for wound healing that acts via inhibition of β-catenin in keratinocytes and by activation of Nrf2 in wound-induced inflammation.

scholarly journals A Novel Chemically Modified Curcumin “Normalizes” Wound-Healing in Rats with Experimentally Induced Type I Diabetes: Initial Studies

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yazhou Zhang ◽  
Steve A. McClain ◽  
Hsi-Ming Lee ◽  
Muna S. Elburki ◽  
Huiwen Yu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Type I Diabetes ◽  
Diabetic Rats ◽  
Limb Amputation ◽  
Type I ◽  
Impaired Wound Healing ◽  
Chemically Modified ◽  
Vehicle Treatment ◽  
Life Threatening

Introduction. Impaired wound-healing in diabetics can lead to life-threatening complications, such as limb amputation, associated in part with excessive matrix metalloproteinase- (MMP-) mediated degradation of collagen and other matrix constituents. In the current study, a novel triketonic chemically modified curcumin, CMC2.24, was tested for efficacy in healing of standardized skin wounds in streptozotocin-induced diabetic rats. Initially, CMC2.24 was daily applied topically at 1% or 3% concentrations or administered systemically (oral intubation; 30 mg/kg); controls received vehicle treatment only. Over 7 days, the diabetics exhibited impaired wound closure, assessed by gross and histologic measurements, compared to the nondiabetic controls. All drug treatments significantly improved wound closure with efficacy ratings as follows: 1% 2.24 > systemic 2.24 > 3% 2.24 with no effect on the severe hyperglycemia. In subsequent experiments, 1% CMC2.24 “normalized” wound-healing in the diabetics, whereas 1% curcumin was no more effective than 0.25% CMC2.24, and the latter remained 34% worse than normal. MMP-8 was increased 10-fold in the diabetic wounds and topically applied 1% (but not 0.25%) CMC2.24 significantly reduced this excessive collagenase-2; MMP-13/collagenase-3 did not show significant changes. Additional studies indicated efficacy of 1% CMC2.24 over more prolonged periods of time up to 30 days.

scholarly journals Bee Venom in Wound Healing

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 148
Author(s):  
Anna Kurek-Górecka ◽  
Katarzyna Komosinska-Vassev ◽  
Anna Rzepecka-Stojko ◽  
Paweł Olczyk
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Healing Process ◽  
Bee Venom ◽  
Epidermal Keratinocytes ◽  
Wound Healing Process ◽  
Diabetic Patients ◽  
Type I ◽  
Impaired Wound Healing

Bee venom (BV), also known as api-toxin, is widely used in the treatment of different inflammatory diseases such as rheumatoid arthritis or multiple sclerosis. It is also known that BV can improve the wound healing process. BV plays a crucial role in the modulation of the different phases of wound repair. It possesses anti-inflammatory, antioxidant, antifungal, antiviral, antimicrobial and analgesic properties, all of which have a positive impact on the wound healing process. The mentioned process consists of four phases, i.e., hemostasis, inflammation, proliferation and remodeling. The impaired wound healing process constitutes a significant problem especially in diabetic patients, due to hypoxia state. It had been found that BV accelerated the wound healing in diabetic patients as well as in laboratory animals by impairing the caspase-3, caspase-8 and caspase-9 activity. Moreover, the activity of BV in wound healing is associated with regulating the expression of transforming growth factor (TGF-β1), vascular endothelial growth factor and increased collagen type I. BV stimulates the proliferation and migration of human epidermal keratinocytes and fibroblasts. In combination with polyvinyl alcohol and chitosan, BV significantly accelerates the wound healing process, increasing the hydroxyproline and glutathione and lowering the IL-6 level in wound tissues. The effect of BV on the wounds has been proved by numerous studies, which revealed that BV in the wound healing process brings about a curative effect and could be applied as a new potential treatment for wound repair. However, therapy with bee venom may induce allergic reactions, so it is necessary to assess the existence of the patient’s hypersensitivity to apitoxin before treatment.

scholarly journals Investigating potential wound healing properties of polysaccharides extracted from Grewia mollis Juss. and Hoheria populnea A. Cunn. (Malvaceae)

2020 ◽  
Author(s):  
N Pearman ◽  
SR Moxon ◽  
Susan Carnachan ◽  
ME Cooke ◽  
EI Nep ◽  
...  
Keyword(s):  
Wound Healing ◽  
Traditional Medicine ◽  
Quantitative Pcr ◽  
Wound Closure ◽  
Type I Collagen ◽  
Type I ◽  
Closure Rate ◽  
Scratch Assay ◽  
Grewia Gum ◽  
Positive Effect

© 2019 Elsevier Ltd The Malvaceae family is a group of flowering plants that include approximately 244 genera, and 4225 species. Grewia mollis, and Hoheria populnea (lacebark), are examples of the Malvaceae family that are used in traditional medicine. For this study polysaccharide samples were extracted from the inner bark of Grewia mollis (unmodified (GG) and destarched grewia gum (GGDS)) and from the leaves of Hoheria populnea (lacebark polysaccharide (LB)). Wound healing properties of grewia gum and lacebark polysaccharides were investigated using 3T3 fibroblast cells cultured in supplemented DMEM. Deposition of collagen using van Gieson's stain, expression of the COL1A1 gene which encodes type I collagen using quantitative PCR, and chemotaxis using a scratch plate assay were analysed following treatment of cells with the test polysaccharides. Quantitative PCR results indicated that all three polysaccharides increased the levels of COL1A1 mRNA, with GG showing the greatest fold change. Histological staining also indicated that the fibroblasts treated with GG deposited more collagen than control cells. Additionally, scratch assay data indicated that simulated cell ‘wounds’ treated with each polysaccharide showed increased wound closure rate over a 36 h period post treatment, with GG exhibiting the greatest effect on wound closure. Analysis of the Malvaceae derived polysaccharides indicates that they could have a positive effect on mechanisms that are integral to wound healing, potentially providing greater scientific understanding behind their use in traditional medicine.

Comparison of the ficus for the wound healing activity in various species

2020 ◽  
Vol 10 (4) ◽  
pp. 67-70
Author(s):  
Mothilal K ◽  
Akila CR ◽  
Mahender K ◽  
Chaitanya Kumar K ◽  
Ravi D
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Subcutaneous Tissue ◽  
Significant Activity ◽  
Herbal Extracts ◽  
Standard Drug ◽  
Excision Wound ◽  
Injuries And Wounds ◽  
Skin Conditions ◽  
Wound Healing Activity

Injuries and wounds are any sorts of damage to the skin or subcutaneous tissue. Usually, any wounds of such sorts are self-healed. Sometimes, there may be a delay in healing, and that delay is caused due to the functional delays in various processes of wound healing. All the Ficus plants show similar activities like the antioxidant, anti-inflammatory and wound healing properties 7including skin conditions like ulcers and rheumatism. The anthelmintic property and immunomodulatory are also seen. The herbal extracts of the same family of Ficus in different plants were investigated for the wound healing activity in the excision wound method, and the extracts showed significant activity compared to the drug. All the extracts showed a better healing ability, but the extract of FBO-100 showed the highest activity followed by FMO followed by FHO and finally the FRO. Overall, the activity of the extract ointment was comparable and was significant compared to the standard drug ointment. The wound closure of the extract ointment treated groups were better and were completed in 12 days, and the activity was more than 96%. The herbal extracts of the same family of Ficus in different plants were investigated for the wound healing activity in the excision wound method, and the extracts showed significant activity compared to the drug. The plants of microcarpa, benghalensis, religiosa and hispida are compared for the activity, and the order showed for the activity was FBO>FMO>FHO>FRO.

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