scholarly journals Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adenosine Receptor Mediated Wnt/β-Catenin Pathway Stimulation by Regulating GSK3b Activity

2021 ◽  
Vol 22 (11) ◽  
pp. 5571
Author(s):  
Jaeyoon Kim ◽  
Jae Young Shin ◽  
Yun-Ho Choi ◽  
So Young Lee ◽  
Mu Hyun Jin ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Protein Kinase ◽  
Adenosine Receptor ◽  
Healing Process ◽  
Tissue Remodeling ◽  
Dermal Fibroblasts ◽  
Wound Healing Process ◽  
Mitochondrial Energy Metabolism ◽  
Wide Range

Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A, A2B and PKA. As a result of Wnt/β-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFβ) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/β-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds.

scholarly journals Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure

2021 ◽  
Vol 14 (4) ◽  
pp. 301
Author(s):  
Yayoi Kawano ◽  
Viorica Patrulea ◽  
Emmanuelle Sublet ◽  
Gerrit Borchard ◽  
Takuya Iyoda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Weight ◽  
Wound Healing ◽  
Hyaluronic Acid ◽  
Healing Process ◽  
Dermal Fibroblasts ◽  
Water Soluble ◽  
Wound Healing Process ◽  
And Migration ◽  
Proliferation And Migration

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.

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

Studies on Wound Healing: Effects of Calcium D-Pantothenate on the Migration, Proliferation and Protein Synthesis of Human Dermal Fibroblasts in Culture

1999 ◽  
Vol 69 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Weimann ◽  
Hermann
Keyword(s):  
Wound Healing ◽  
Protein Synthesis ◽  
Healing Process ◽  
Dermal Fibroblasts ◽  
Wound Healing Process ◽  
Human Dermal Fibroblasts ◽  
The Mean ◽  
Cell Densities ◽  
Migration Of Cells ◽  
Wounded Area

The effect of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts from three different donors was investigated. The migration of cells into a wounded area was dose-dependently stimulated by Ca D-pantothenate. The number of cells that migrated across the edge of the wound increased from 32 ± 7 cells/ mm without Ca D-pantothenate to 76 ± 2 cells/ mm with 100 mg/ml Ca D-pantothenate. Moreover, the mean migration distance per cell increased from 0.23 ± 0.05 mm to 0.33 ± 0.02 mm. The mean migration speed was calculated to be 10.5 mm/hour without and 15 mm/hour with Ca D-pantothenate. Cell proliferation was also dose-dependently stimulated. The final cell densities were 1.2 to 1.6-fold higher in cultures containing 100 mg/ml Ca D-pantothenate. The protein synthesis was modulated, since two unidentified proteins were more strongly expressed in pantothenate supplemented cultures. In conclusion, Ca D-pantothenate accelerates the wound healing process by increasing the number of migrating cells, their distance and hence their speed. In addition, cell division is increased and the protein synthesis changed. These results suggest that higher quantities of pantothenate are locally required to enhance 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.

scholarly journals The Wound Healing Potential of Aspilia africana (Pers.) C. D. Adams (Asteraceae)

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Richard Komakech ◽  
Motlalepula Gilbert Matsabisa ◽  
Youngmin Kang
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Antioxidant Activities ◽  
Healing Process ◽  
Flowering Plant ◽  
Wound Healing Process ◽  
Integral Role ◽  
Low Toxicity

Wounds remain one of the major causes of death worldwide. Over the years medicinal plants and natural compounds have played an integral role in wound treatment. Aspilia africana (Pers.) C. D. Adams which is classified among substances with low toxicity has been used for generations in African traditional medicine to treat wounds, including stopping bleeding even from severed arteries. This review examined the potential of the extracts and phytochemicals from A. africana, a common herbaceous flowering plant which is native to Africa in wound healing. In vitro and in vivo studies have provided strong pharmacological evidences for wound healing effects of A. africana-derived extracts and phytochemicals. Singly or in synergy, the different bioactive phytochemicals including alkaloids, saponins, tannins, flavonoids, phenols, terpenoids, β-caryophyllene, germacrene D, α-pinene, carene, phytol, and linolenic acid in A. africana have been observed to exhibit a very strong anti-inflammatory, antimicrobial, and antioxidant activities which are important processes in wound healing. Indeed, A. africana wound healing ability is furthermore due to the fact that it can effectively reduce wound bleeding, hasten wound contraction, increase the concentration of basic fibroblast growth factor (BFGF) and platelet derived growth factor, and stimulate the haematological parameters, including white and red blood cells, all of which are vital components for the wound healing process. Therefore, these facts may justify why A. africana is used to treat wounds in ethnomedicine.

Use of bromelain in cutaneous wound healing in streptozocin-induced diabetic rats: an experimental model

2020 ◽  
Vol 29 (9) ◽  
pp. 488-495
Author(s):  
Amene Nikgoftar Fathi ◽  
Mohammad Hassan Sakhaie ◽  
Sepehr Babaei ◽  
Soroush Babaei ◽  
Fateme Slimabad ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Diabetic Rats ◽  
Wound Healing Process ◽  
Wound Area ◽  
Small Vessels ◽  
Histological Sections ◽  
Therapeutic Benefits ◽  
Wide Range

Objective: To assess the effect of bromelain on different aspects of the wound healing process in type 1 diabetic rats. Method: In this study, 112 streptozocin-diabetic (type 1) male Wistar rats were euthanised; 28 each on days three, five, seven and 15, after a wound incision had been made. To estimate changes in a number of different cellular and tissue elements, histological sections were provided from all wound areas and stained with haematoxylin and eosin. Some 1.056mm2 of total wound area from all specimens were evaluated, by assessment of 4200 microscope photos provided from all histological sections, by stereological methods. A biomechanical test of each wound area was performed with an extensometer to evaluate the work-up to maximum force and maximum stress of the healed wound on day 15. Results: In the experimental groups, bromleain caused significant wound contraction and reduced granulation tissue formation by day 7 (p=0.003); increased neovasculars (new small vessels that appear in the wound area during wound healing) on days three, five and seven (p=0.001); significantly increased fibroblasts on day five but decreased by day seven (p=0.002); and significantly decreased macrophage numbers and epithelium thickness on all days of study (p=0.005). Wound strength significantly increased in experimental groups by day 15. Conclusion: Bromelain has a wide range of therapeutic benefits, but in most studies the mode of its action is not properly understood. It has been proved that bromelain has no major side effects, even after prolonged use. According to the results of this study, bromelain can be used as an effective health supplement to promote and accelerate wound healing indices, reduce inflammation and improve biomechanical parameters in diabetic wounds.

Micronutrients and Natural Compounds Status and Their Effects on Wound Healing in the Diabetic Foot Ulcer

2017 ◽  
Vol 16 (4) ◽  
pp. 244-250 ◽  
Author(s):  
Kanokwan Kulprachakarn ◽  
Sakaewan Ounjaijean ◽  
Jukkrit Wungrath ◽  
Raj Mani ◽  
Kittipan Rerkasem
Keyword(s):  
Wound Healing ◽  
Diabetic Foot ◽  
Healing Process ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Herbal Remedies ◽  
Current Evidence ◽  
Wound Healing Process ◽  
Impaired Wound Healing ◽  
Wide Range

The diabetic foot ulcer (DFU) is an invariably common complication of diabetes mellitus, it is also a significant cause of amputation as well as extended hospitalization. As most patients with DFU suffer from malnutrition, which has been related to improper metabolic micronutrients status, alterations can affect impaired wound healing process. Micronutrients and herbal remedies applications present a wide range of health advantages to patients with DFU. The purpose of this review is to provide current evidence on the potential effect of dietary supplementations such as vitamins A, C, D, E, magnesium, zinc, copper, iron, boron, and such naturally occurring compounds as Aloe vera, Naringin, and Radix Astragali (RA) and Radix Rehmanniae (RR) in the administration of lower extremity wounds, especially in DFU, and to present some insights for applications in the treatment of DFU patients in the future.

scholarly journals Effect of Hypoxia on Gene Expression in Cell Populations Involved in Wound Healing

2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Sarah D’Alessandro ◽  
Andrea Magnavacca ◽  
Federica Perego ◽  
Marco Fumagalli ◽  
Enrico Sangiovanni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Endothelial Cells ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Healing Process ◽  
Critical Role ◽  
Dermal Fibroblasts ◽  
Cell Populations ◽  
Wound Healing Process

Wound healing is a complex process regulated by multiple signals and consisting of several phases known as haemostasis, inflammation, proliferation, and remodelling. Keratinocytes, endothelial cells, macrophages, and fibroblasts are the major cell populations involved in wound healing process. Hypoxia plays a critical role in this process since cells sense and respond to hypoxic conditions by changing gene expression. This study assessed the in vitro expression of 77 genes involved in angiogenesis, metabolism, cell growth, proliferation and apoptosis in human keratinocytes (HaCaT), microvascular endothelial cells (HMEC-1), differentiated macrophages (THP-1), and dermal fibroblasts (HDF). Results indicated that the gene expression profiles induced by hypoxia were cell-type specific. In HMEC-1 and differentiated THP-1, most of the genes modulated by hypoxia encode proteins involved in angiogenesis or belonging to cytokines and growth factors. In HaCaT and HDF, hypoxia mainly affected the expression of genes encoding proteins involved in cell metabolism. This work can help to enlarge the current knowledge about the mechanisms through which a hypoxic environment influences wound healing processes at the molecular level.

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