scholarly journals Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible Factor- (HIF-) 1 Signalling

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Shuo Qiu ◽  
Yachao Jia ◽  
Yunchu Sun ◽  
Pei Han ◽  
Jia Xu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Rat Model ◽  
Healing Process ◽  
Wound Healing Process ◽  
Type I ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Vhl Protein

Aims. The purpose of the present research is to investigate the effects of the VHL protein antagonist, VH298, on functional activities of fibroblasts and vascular endothelial cells and the effects on the wound healing process in a streptozotocin-induced hyperglycaemic rat model. Methods. HIF-1α and hydroxy-HIF-1α protein levels in VH298-treated rat fibroblasts (rFb) were measured by immunoblotting, rFb proliferation was detected by the CCK-8 assay, and mRNA levels of related genes were measured by quantitative RT-PCR. In vitro wound healing was simulated by the scratch test; angiogenesis was measured by the human umbilical vein endothelial cell (hUVEC) tube formation assay. VH298 or PBS was locally injected into wounds in rat models with streptozotocin- (STZ-) induced hyperglycaemia, the wound tissues were harvested, and haematoxylin-eosin (HE) and Masson trichrome staining and immunohistochemical processes were conducted. Results. HIF-1α and hydroxy-HIF-1α levels increased in VH298-treated rFb, in a time- and dose-dependent manner. Thirty micromolar VH298 could significantly increase cell proliferation, angiogenesis, and gene expression of type I collagen-α1 (Col1-α1), vascular endothelial growth factor A (VEGF-A), and insulin-like growth factor 1 (IGF-1). The VH298-treated wound had a better healing pattern, activation of HIF-1 signalling, and vascularization. Conclusions. Taken together, VH298 activated the HIF-1 signalling pathway by stabilizing both HIF-1α and hydroxy-HIF-1α. VH298 enhanced rFb functions, promoted hUVEC angiogenesis, and accelerated wound healing in the rat model mimicking diabetes mellitus.

Glucocorticoid-induced contractility and F-actin content of human lung fibroblasts in three-dimensional culture

2000 ◽  
Vol 278 (1) ◽  
pp. L13-L18 ◽  
Author(s):  
Hiroyuki Miki ◽  
Tadashi Mio ◽  
Sonoko Nagai ◽  
Yuma Hoshino ◽  
Takeo Tsutsumi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Human Lung ◽  
Healing Process ◽  
Lung Fibroblast ◽  
Lung Fibroblasts ◽  
Wound Healing Process ◽  
Architectural Distortion ◽  
Type I ◽  
Dependent Manner ◽  
Human Lung Fibroblast

Fibroblast contractility plays a useful role in the wound healing process but contributes to architectural distortion in the lungs. Glucocorticoids (GCs) have been reported to reduce dermal fibroblast contractility, which may result in delaying wound healing, but the effects on lung fibroblasts are unknown. In this study, we examined how human lung fibroblast contractility is altered in the presence of GCs. Lung fibroblast cell lines ( n = 5) were established from normal parts of surgically resected lung tissue. The effects of GCs on contractility were investigated with a type I collagen gel contraction assay. Filamentous actin (F-actin) content was detected by confocal microscopy and measured with a fluorescent phalloidin binding assay. GCs augmented fibroblast contraction in a concentration-dependent manner, with an approximate EC50 of 1.8 × 10−8 M, whereas other steroid derivatives had no effects. GC contractility needed de novo protein synthesis. The GC-induced increase in contractility was found to be consistent with an increase in F-actin content. In conclusion, lung fibroblast contractility was enhanced with GCs through an upregulation of lung fibroblast F-actin.

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 Increased Vascular Endothelial Growth Factor (VEGF) Expression in Wistar Rat Oral Mucosa Traumatic Ulcer due to Golden Sea Cucumber (Stichopus hermanni) Extract Gel

2019 ◽  
Vol 53 (6) ◽  
Author(s):  
Pratiwi Soesilawati ◽  
Eghia Laditra Ambarani ◽  
Yuliati ◽  
Aqsa Sjuhada Oki
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Wound Healing ◽  
Growth Factor ◽  
Sea Cucumber ◽  
Healing Process ◽  
Control Group ◽  
Wound Healing Process ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor

Background. Traumatic ulcer is a lesion formed by a local tissue damage due to trauma on epithelial layer. Vascular Endothelial Growth Factor (VEGF) plays an important role in wound healing, especially in angiogenesis. Golden sea cucumber (Stichopus hermanni) is believed to accelerate the wound healing process. Objective. To prove that golden sea cucumber extract can increase VEGF expression in oral mucous membrane traumatic ulcer in rat.Method. S. hermanni extract was prepared by freeze-dry method, then an extract was made using PEG 400 or PEG 4000 at 40% and 80% concentrations, respectively, and applied to the animal’s oral wounds. The animals were divided into three groups: control; 40% S. hermanni extract gel; and 80% S. hermanni extract gel. The ulcers that formed on day 3 were rubbed gently with S. hermanni extract gel. After being sacrificed on day 4, sample tissues from the lower lips were prepared for histopathology to count the number of VEGF expression. The results were analyzed using the One-Way ANOVA statistical test. Results. A significant increase in the VEGF expression of 80% concentration S. hermanni extract gel was found compared with those in the control group (p=0.00). Conclusion. Golden sea cucumber extract (Stichopus hermanni) gel increased the VEGF expression in oral mucous traumatic ulcer.

Biological activities of novel lipid mediator sphingosine 1-phosphate in rat hepatic stellate cells

2000 ◽  
Vol 279 (2) ◽  
pp. G304-G310 ◽  
Author(s):  
Hitoshi Ikeda ◽  
Yutaka Yatomi ◽  
Mikio Yanase ◽  
Hiroaki Satoh ◽  
Hisato Maekawa ◽  
...  
Keyword(s):  
Wound Healing ◽  
Hepatic Stellate Cells ◽  
Biological Activities ◽  
Healing Process ◽  
Stellate Cells ◽  
Mitogen Activated Protein Kinase ◽  
Lipid Mediator ◽  
Wound Healing Process ◽  
Mrna Levels ◽  
Sphingosine 1 Phosphate

Sphingosine 1-phosphate (S-1-P), a lipid mediator shown to be a ligand for G protein-coupled receptors (AGRs), endothelial differentiation gene (EDG)1, EDG3, and AGR16/EDG5, is stored in platelets and released on their activation. Platelet consumption occurs in acute liver injury. Hepatic stellate cells (HSCs) play an important role in wound healing. Effects of S-1-P on HSCs were investigated. S-1-P enhanced proliferation of culture-activated HSCs. The mitogenic effect was pertussis toxin sensitive, mitogen-activated protein kinase dependent, and more prominent at lower cell density. S-1-P increased contraction of collagen lattices containing HSCs, irrespective of activation state, in a C3 exotoxin-sensitive manner. mRNAs of EDG1 and AGR16, but not of EDG3, were detected in HSCs. In HSC activation, EDG1 mRNA levels were downregulated, whereas AGR16 mRNA levels were unchanged. Considering that HSCs are capable of production of extracellular matrices and modulation of blood flow in sinusoids, our results suggest that S-1-P may play a role in wound healing process in the liver.

Transforming growth factor-? isoforms differently stimulate pro?2 (I) collagen gene expression during wound healing process in transgenic mice

2002 ◽  
Vol 190 (3) ◽  
pp. 375-381 ◽  
Author(s):  
Takuro Kinbara ◽  
Fumiaki Shirasaki ◽  
Shigeru Kawara ◽  
Yutaka Inagaki ◽  
Benoit de Crombrugghe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Wound Healing Process ◽  
Collagen Gene ◽  
Collagen Gene Expression

scholarly journals Effect of Amniotic Fluid Stem Cells and Amniotic Fluid Cells on the Wound Healing Process in a White Rat Model

2013 ◽  
Vol 40 (5) ◽  
pp. 496 ◽  
Author(s):  
Jung Dug Yang ◽  
Dong Sik Choi ◽  
Young Kyoo Cho ◽  
Taek Kyun Kim ◽  
Jeong Woo Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Amniotic Fluid ◽  
Rat Model ◽  
Healing Process ◽  
Wound Healing Process ◽  
Amniotic Fluid Stem Cells ◽  
Amniotic Fluid Cells

scholarly journals Collagen extract obtained from Nile tilapia (Oreochromis niloticus L.) skin accelerates wound healing in rat model via up regulating VEGF, bFGF, and α-SMA genes expression

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Zizy I. Elbialy ◽  
Ayman Atiba ◽  
Aml Abdelnaby ◽  
Ibrahim I. Al-Hawary ◽  
Ahmed Elsheshtawy ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Rat Model ◽  
Nile Tilapia ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Control Group ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Genes Expression

Abstract Background Collagen is the most abundant structural protein in the mammalian connective tissue and represents approximately 30% of animal protein. The current study evaluated the potential capacity of collagen extract derived from Nile tilapia skin in improving the cutaneous wound healing in rats and investigated the underlying possible mechanisms. A rat model was used, and the experimental design included a control group (CG) and the tilapia collagen treated group (TCG). Full-thickness wounds were conducted on the back of all the rats under general anesthesia, then the tilapia collagen extract was applied topically on the wound area of TCG. Wound areas of the two experimental groups were measured on days 0, 3, 6, 9, 12, and 15 post-wounding. The stages of the wound granulation tissues were detected by histopathologic examination and the expression of vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-ß1) were investigated using immunohistochemistry. Moreover, relative gene expression analysis of transforming growth factor-beta (TGF-ß1), basic fibroblast growth factor (bFGF), and alpha-smooth muscle actin (α-SMA) were quantified by real-time qPCR. Results The histopathological assessment showed noticeable signs of skin healing in TCG compared to CG. Immunohistochemistry results revealed remarkable enhancement in the expression levels of VEGF and TGF-β1 in TCG. Furthermore, TCG exhibited marked upregulation in the VEGF, bFGF, and α-SMA genes expression. These findings suggested that the topical application of Nile tilapia collagen extract can promote the cutaneous wound healing process in rats, which could be attributed to its stimulating effect on recruiting and activating macrophages to produce chemotactic growth factors, fibroblast proliferation, and angiogenesis. Conclusions The collagen extract could, therefore, be a potential biomaterial for cutaneous wound healing therapeutics.

scholarly journals Glucagon-Like Peptide-2 Analogue ZP1849 Augments Colonic Anastomotic Wound Healing

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Marie Kjaer ◽  
Wayne Russell ◽  
Peter Schjerling ◽  
Elena Cottarelli ◽  
Kennet N. Christjansen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Breaking Strength ◽  
Target Area ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Soluble Collagen ◽  
Cox 2 ◽  
Glucagon Like Peptide

Background. The enteroendocrine hormone glucagon-like peptide- (GLP-) 2 is a potent trophic factor in the gastrointestinal tract. The GLP-2 receptor (GLP-2R) is expressed in the stroma of the large bowel wall, which is the major therapeutic target area to prevent anastomotic leakage. We investigated the efficacy of the long-acting GLP-2 analogue ZP1849 on colonic anastomotic wound healing. Methods. Eighty-seven male Wistar rats were stratified into four groups and received daily treatment with vehicle or ZP1849 starting one day before (day -1) end-to-end anastomosis was constructed in the left colon on day 0, and on days 0 (resected colon segment), 3, and 5, gene expressions of GLP-2R, Ki67, insulin-like growth factor- (IGF-) 1, type I (COL1A1) and type III (COL3A1) procollagens, cyclooxygenase- (COX-) 1, COX-2, and matrix metalloproteinase- (MMP-) 7 were quantified by RT-qPCR. Breaking strength, myeloperoxidase (MPO), transforming growth factor- (TGF-) β1, and soluble collagen proteins were measured on days 3 and 5. Results. ZP1849 treatment increased Ki67 (P<0.0001) and IGF-1 (P<0.05) mRNA levels in noninjured colon day 0, and postoperatively in the anastomotic wounds compared to vehicle-treated rats. ZP1849-treated rats had increased (P=0.042) anastomotic breaking strength at day 5 compared with vehicle. COL1A1 and COL3A1 mRNA levels (P<0.0001) and soluble collagen proteins (P<0.05) increased from day 3 to day 5 in ZP1849-treated rats, but not in vehicle-treated rats. COX-2 mRNA and MPO protein levels decreased from day 3 to day 5 (P<0.001) in both groups. ZP1849 treatment reduced TGF-β1 protein levels on day 5 (P<0.001) but did not impact MMP-7 transcription. Conclusions. The GLP-2 analogue ZP1849 increased breaking strength, IGF-1 expression, and cell proliferation, which may be beneficial for colonic anastomotic wound healing.

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.

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