scholarly journals B2 agonist (Salbutamol) modulate skin wound healing processes

Author(s):  
Fahim M. Mahmood ◽  
Hayder B. Sahib ◽  
Khalid W. Qassim

Wound healing is a complex physiological and dynamic process required the coordination of numerous cell types and biological processes to regenerate damaged tissue and initiate repair which is dependent on a number of inter-related factors. This study was aimed to demonstrate whether the ?2 receptor has role in wound healing and angiogenesis. A murine wild-type (in vivo), excisional skin wound model was done to demonstrate that activation of ?2AR delay wound repair, twenty-four male albino mice were used to investigate the effect of the drug on experimental wound healing grossly, histo-pathologically and immune-histochemically compared with vehicle-only controls. The results showed that the rate of wound healing was significantly slower in salbutamol group than in control group (P

2018 ◽  
Vol 49 (3) ◽  
pp. 1074-1089 ◽  
Author(s):  
Ying Zhao ◽  
Qiang Wang ◽  
Yuan Jin ◽  
Yadan Li ◽  
Changjun Nie ◽  
...  

Background/Aims: How to aid recovery from severe skin injuries, such as burns, chronic or radiation ulcers, and trauma, is a critical clinical problem. Current treatment methods remain limited, and the discovery of ideal wound-healing therapeutics has been a focus of research. Functional recombinant proteins such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have been developed for skin repair, however, some disadvantages in their use remain. This study reports the discovery of a novel small peptide targeting fibroblast growth factor receptor 2 IIIc (FGFR2IIIc) as a potential candidate for skin wound healing. Methods: A phage-displayed peptide library was used for biopanning FGFR2IIIc-targeting small peptides. The selected small peptides binding to FGFR2IIIc were qualitatively evaluated by an enzyme-linked immunosorbent assay. Their biological function was detected by a cell proliferation assay. Among them, an optimized small peptide named H1 was selected for further study. The affinity of the H1 peptide and FGFR2IIIc was determined by an isothermal titration calorimetry device. The ability of theH1 peptide to promote skin wound repair was investigated using an endothelial cell tube formation assay and wound healing scratch assay in vitro. Subsequently, the H1 peptide was assessed using a rat skin full-thickness wound model and chorioallantoic membrane (CAM) assays in vivo. To explore its molecular mechanisms, RNA-Seq, quantitative real-time PCR, and western blot assays were performed. Computer molecular simulations were also conducted to analyze the binding model. Results: We identified a novel FGFR2IIIc-targeting small peptide, called H1, with 7 amino acid residues using phage display. H1 had high binding affinity with FGFR2IIIc. The H1 peptide promoted the proliferation and motility of fibroblasts and vascular endothelial cells in vitro. In addition, the H1 peptide enhanced angiogenesis in the chick chorioallantoic membrane and accelerated wound healing in a rat full-thickness wound model in vivo. The H1 peptide activated both the PI3K-AKT and MAPK-ERK1/2 pathways and simultaneously increased the secretion of vascular endothelial growth factor. Computer analysis demonstrated that the model of H1 peptide binding to FGFR2IIIc was similar to that of FGF2 and FGFR2IIIc. Conclusion: The H1 peptide has a high affinity for FGFR2IIIc and shows potential as a wound healing agent. As a substitute for bFGF, it could be developed into a novel therapeutic candidate for skin wound repair in the future.


2015 ◽  
Vol 36 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Bizunesh M. Borena ◽  
Ann Martens ◽  
Sarah Y. Broeckx ◽  
Evelyne Meyer ◽  
Koen Chiers ◽  
...  

Mammal skin has a crucial function in several life-preserving processes such as hydration, protection against chemicals and pathogens, initialization of vitamin D synthesis, excretion and heat regulation. Severe damage of the skin may therefore be life-threatening. Skin wound repair is a multiphased, yet well-orchestrated process including the interaction of various cell types, growth factors and cytokines aiming at closure of the skin and preferably resulting in tissue repair. Regardless various therapeutic modalities targeting at enhancing wound healing, the development of novel approaches for this pathology remains a clinical challenge. The time-consuming conservative wound management is mainly restricted to wound repair rather than restitution of the tissue integrity (the so-called “restitutio ad integrum”). Therefore, there is a continued search towards more efficacious wound therapies to reduce health care burden, provide patients with long-term relief and ultimately scarless wound healing. Recent in vivo and in vitro studies on the use of skin wound regenerative therapies provide encouraging results, but more protracted studies will have to determine whether the effect of observed effects are clinically significant and whether regeneration rather than repair can be achieved. For all the aforementioned reasons, this article reviews the emerging field of regenerative skin wound healing in mammals with particular emphasis on growth factor- and stem cell-based therapies.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kareem Abdelsaid ◽  
Sudhahar Varadarajan ◽  
Archita Das ◽  
Yutao Liu ◽  
Xuexiu Fang ◽  
...  

Background: Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) have detrimental effects. Exercise not only improves endothelial dysfunction and angiogenesis in T2DM but also induces secretion of exosomes into circulation. Extracellular superoxide dismutase (ecSOD) is a major secretory Cu containing antioxidant enzyme that catalyzes dismutation of O 2 •- to H 2 O 2 and its full activity requires Cu transporter ATP7A. We reported that ecSOD-derived H 2 O 2 in endothelial cells (ECs) enhances angiogenesis while impaired ATP7A-ecSOD axis in diabetes induces endothelial dysfunction. Here we examined whether exercise-derived exosomes (Exe-Exo) may have pro-angiogenic effects via regulating ATP7A-ecSOD axis in T2DM. Results: Two weeks of voluntary wheel exercise of control C57Bl6 mice increased plasma exosome levels (6.2-fold) characterized by Nanosight, TEM and exosome markers (CD63, CD81, Tsg101). Treatment of HUVECs with equal number of exosomes revealed that angiogenic responses such as EC migration (1.8-fold) and tube formation (1.7-fold) were significantly enhanced by Exe-Exo compared to sedentary-derived exosomes (Sed-Exo). This was associated with increased ATP7A (2.9-fold) and ecSOD (1.4-fold) expression in Exe-Exo. Sed-Exo from high fat-induced T2DM mice significantly decreased EC migration (40%) and tube formation (10%) as well as ATP7A expression (28%) compared to Sed-Exo from control mice, which were restored by T2DM Exe-Exo, but not by T2DM/ecSOD KO Exe-Exo. Furthermore, exosomes overexpressing ecSOD (ecSOD-Exo) which mimic exercise increased angiogenesis and H2O2 levels in ECs, which were inhibited by overexpression of catalase. In vivo, skin wound healing model showed that direct application of T2DM Sed-Exo delayed while T2DM Exe-Exo enhanced wound healing of control mice. Furthermore, defective wound healing in T2DM mice or ecSOD KO mice were rescued by ecSOD-Exo application. Conclusion: Exercise training improves pro-angiogenic function of circulating exosomes in T2DM via increasing ATP7A-ecSOD axis, which may provide an effective therapy for promoting angiogenesis and wound repair in metabolic and cardiovascular diseases.


2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.


2020 ◽  
Vol 8 ◽  
Author(s):  
Pengcheng Xu ◽  
Yaguang Wu ◽  
Lina Zhou ◽  
Zengjun Yang ◽  
Xiaorong Zhang ◽  
...  

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.


2021 ◽  
Vol 12 (4) ◽  
pp. 594-598
Author(s):  
S. B. Pavlov ◽  
O. B. Litvinova ◽  
N. M. Babenko

Chronic kidney disease negatively affects the morphofunctional state of all organs due to hemodynamic and metabolic disorders. Changes in the content of cytokines observed in kidney diseases, which regulate the processes of inflammation and tissue repair, can complicate the course of the wound process. This research aimed to study disorders in the process of skin wound repair due to changes in the dynamics of production of interleukins IL-1β, IL-6, IL-10, IL-4, growth factors bFGF and VEGF in animals with experimental chronic kidney disease. The levels of interleukins and growth factors were determined on the 7th, 14th and 28th days after surgical modeling of wounds in the blood of rats with experimental chronic kidney disease and animals of the control group. To assess the dynamics and quality of wound healing, a semi-quantitative histological analysis was performed. The study showed an increase in the content of pro-inflammatory interleukins in the group of sick rats: on the 7th day the level of IL-1β was 1.19 times higher, and IL-6 – 1.55 times, on the 14th day the level of IL-1β was 1.37 times in comparison with the control group. The maximum increase in the concentration of anti-inflammatory interleukins was noted on the 28th day: IL-4 was 2.10 times higher, IL-10 – 1.39 times higher than in the control group. The content of bFGF and VEGF in animals of the control group reached its maximum on the 7th day, and in animals with chronic kidney disease – on the 15th day after surgery. Semi-quantitative histological analysis showed a decrease in indicators in the group of sick animals: the number of fibroblasts and collagen deposition – on the 7th day, reepithelialization – on the 28th day. A persistent increase in the number of polymorphonuclear leukocytes was also noted at all periods of the experiment: by 1.38, 1.99, and 9.82 times – on the 7th, 14th, and 28th days, respectively. The study showed that the dynamics of the production of interleukins and growth factors were impaired in rats with chronic kidney disease. In the process of damage regeneration in sick animals, pro-inflammatory mechanisms prevailed with the involvement of a large number of immunocompetent cells, as a result, skin wounds took longer to heal.


2015 ◽  
Vol 4 (4) ◽  
pp. 197-201
Author(s):  
Tetiana A. Krupodorova ◽  
◽  
Pavlo P. Klymenko ◽  
Victor Yu. Barshteyn ◽  
Yuri I. Leonov ◽  
...  

The aqueous extracts of Ganoderma lucidum 1900 (Curtis) P. Karst and Crinipellis schevczenkovi 31 Buchalo mycelia were investigated for skin wound healing activity in vivo using the excision wound healing model. The extracts were prepared by mixing of 100 mg of powdered mycelium of both mushrooms with 1 mL of sterile distilled water for injections. White albino mice line FVB/Cg., 3 months of age (male), were used for the study. The rate of wound healing and the histology of healed wounds in mice have been studied. Visual method of wound study and histological investigation of skin tissue showed the presence of wound healing potential of G. lucidum and C. schevczenkovi mycelia. The wound healing process was expressed more active on 3th day in case of topical application of C. schevczenkovi mycelium extract, but on 5th day the wound healing effects of both mushroom extracts were almost at the same level and statistically better then results in the control group. Wounds treated with mycelial extracts were covered completely on the 6th day compared with 8th day in control group. Wound healing ability of C. schevczenkovi observed in present investigations for the first time.


2012 ◽  
pp. 241-250 ◽  
Author(s):  
P. GÁL ◽  
T. VASILENKO ◽  
I. KOVÁČ ◽  
M. KOSTELNÍKOVÁ ◽  
J. JAKUBČO ◽  
...  

Previously, we found that treatment of cutaneous wounds with Atropa belladonna L. (AB) revealed shortened process of acute inflammation as well as increased tensile strength and collagen deposition in healing skin wounds (Gál et al. 2009). To better understand AB effect on skin wound healing male Sprague-Dawley rats were submitted to one round full thickness skin wound on the back. In two experimental groups two different concentrations of AB extract were daily applied whereas the control group remained untreated. For histological evaluation samples were removed on day 21 after surgery and stained for wide spectrum cytokeratin, collagen III, fibronectin, galectin-1, and vimentin. In addition, in the in vitro study different concentration of AB extract were used to evaluate differences in HaCaT keratinocytes proliferation and differentiation by detection of Ki67 and keratin-19 expressions. Furthermore, to assess ECM formation of human dermal fibroblasts on the in vitro level fibronectin and galectin-1 were visualized. Our study showed that AB induces fibronectin and galectin-1 rich ECM formation in vitro and in vivo. In addition, the proliferation of keratinocytes was also increased. In conclusion, AB is an effective modulator of skin wound healing. Nevertheless, further research is needed to find optimal therapeutic concentration and exact underlying mechanism of action.


2021 ◽  
Vol 12 ◽  
pp. e9-e9
Author(s):  
Abdollah Amini ◽  
Hasan Soleimani ◽  
Fatemehalsadat Rezaei ◽  
Seyed Kamran Ghoreishi ◽  
Sufan Chien ◽  
...  

Introduction: Abnormal wound repair is a cause for considerable expense, as well as patient morbidity and mortality. Here, we investigated the combined impact of photobiomodulation (PBM) and curcumin on a rat experimental model of an acute skin wound. Methods: A round full-thickness wound was created on the back of each rat. We divided the rats into the following four groups. Group one was the control group. Group two received pulse wave (PW) PBM at a dose of 890 nm, 80 Hz, and 0.2 J/cm2 . Group 3 received 40 mg/kg curcumin by gastric gavage and group 4 were treated with PWPBM + curcumin. We measured the wound area on days 4, 7, and 15, and performed microbiological and tensiometric examinations. Results: There was markedly improved wound contraction in the curcumin (7.5 ± 0.57; P=0.000), PBM (8.5 ± 1.2; P=0.000), and PBM + curcumin (14.5 ± 4.3; P=0.002) groups relative to the control group (25 ± 6). PBM (100 ± 7.3; P=0.005), and PBM + curcumin (98 ± 6; P=0.005) groups meaningfully improved tensile strength relative to the control group (61 ± 8.2). On day 15, the PBM (10 ± 5; P=0.000), curcumin (14 ± 4.5, P=0.000), and PBM + curcumin (27.3 ± 8.3; P=0.000) groups meaningfully decreased microbial flora relative to the control group (95 ± 6). Conclusion: We concluded that the PBM and PBM + curcumin groups meaningfully accelerated wound healing of the acute skin wound in the rats. The results of the PBM group were statistically more effective than the curcumin alone and PBM + curcumin-treated groups.


2021 ◽  
pp. 1-10
Author(s):  
Heiko Sorg ◽  
Inga Zwetzich ◽  
Daniel Johannes Tilkorn ◽  
Jonas Kolbenschlag ◽  
Jörg Hauser ◽  
...  

<b><i>Introduction:</i></b> Extracorporeal shock waves (ESWs) have been shown to have a positive effect on skin wound healing; however, little is known on the regeneration of the microcirculation and angiogenesis as well as the different application modes. <b><i>Methods:</i></b> A total of 40 BALB/c mice were provided with dorsal skin fold chambers and were divided into 3 therapy groups (<i>n</i> = 30) and one control group (<i>n</i> = 10). The 3 therapy groups were treated with shock waves at different pulse rates (500–1,000 pulses/min) and application frequencies (day 0 and day 6 or day 0 only). Photographic documentation and intravital microscopy were carried out on day 1, 2, 4, and 6 after wounding. <b><i>Results:</i></b> Using the newly developed Diver Box, shock waves could be applied in vivo without mechanical tissue damage. Shock wave therapy to skin wounds demonstrated to induce faster wound closure rates in the beginning than controls in groups with higher pulse rates and frequencies of the shock waves. Furthermore, the regeneration of microcirculation and perfusion in the healing skin was significantly improved after the application of, in particular, higher pulse rates as given by increased numbers of perfused capillaries and functional vessel density. The study of inflammation showed, especially in high-pulse ESW groups, higher leukocyte counts, and rolling leukocytes over time until day 6 as a response to the induction of inflammatory reaction after ESW application. Angiogenesis showed a marked increase in positive areas as given by sprouts, coils, and recruitments in all ESW groups, especially between days 4 and 6. <b><i>Conclusion:</i></b> The major findings of this trial demonstrate that ESW therapy to skin wounds is effective and safe. This is demonstrated by the initially faster wound closure rate, but later the same wound closure rate in the treatment groups than in controls. Furthermore, during the regeneration of microcirculation and perfusion in the healing skin, a significant improvement was observed after the application of, in particular, higher ESW pulse rates, suggesting an ESW-related increase in nutrient and oxygen supply in the wound tissue.


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