scholarly journals FG-4592 Accelerates Cutaneous Wound Healing by Epidermal Stem Cell Activation via HIF-1α Stabilization

2018 ◽  
Vol 46 (6) ◽  
pp. 2460-2470 ◽  
Author(s):  
Di Tang ◽  
Junhui Zhang ◽  
Tiantian Yan ◽  
Jingyu Wei ◽  
Xupin Jiang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Cell Activation ◽  
Acute Hypoxia ◽  
Healing Process ◽  
Wound Healing Process ◽  
Quiescent State ◽  
Skin Wound Healing ◽  
Western Blots ◽  
Activated State

Background/Aims: Regional hypoxia promptly develops after trauma because of microvascular injury and increased oxygen consumption. This acute hypoxia plays a positive role in early skin wound healing. One of the mechanisms underlying the beneficial effects of acute hypoxia on wound healing may be increased hypoxia-inducible factor-1 (HIF-1α) expression. HIF-1α may affect the wound-healing process through many aspects, including angiogenesis, metabolism, and extra-cellular matrix synthesis and remodelling. Epidermal stem cells (EpSCs) are important participants in wound repair; however, whether these cells are regulated by hypoxia is unclear. This study aimed to elucidate the regulatory mechanism by which hypoxia acts on EpSCs. Methods: CCK8 assays, western blots and live cell station observation were employed to compare the viability, proliferation and motility of EpSCs cultured under normoxic conditions (21% O2) with those cultured under hypoxic conditions (2% O2). Moreover, we used FG-4592 (a prolyl hydroxylase inhibitor that stabilizes HIF-1α in normoxia), KC7F2 (a selective inhibitor of HIF-1α transcription) and siRNA against HIF-1α to regulate HIF-1α expression. Results: Acute hypoxia caused EpSCs to switch from a quiescent state to an activated state with higher viability and motility, as well as an earlier proliferation peak. We demonstrated that the HIF-1 signalling pathway mediated hypoxia-induced activation of EpSCs. Finally, the in vivo experiments showed that exogenous FG-4592 effectively accelerates wound healing, shortens healing times and even induces epidermal hyperplasia. Conclusion: This study demonstrated that both hypoxia and exogenous FG-4592 improve EpSC proliferation and motility by stabilizing HIF-1α, and its results suggest that HIF-1α is an important target through which wound healing can be accelerated and that FG-4592 is a promising new drug for wound repair.

scholarly journals Systemic and topical administration of spermidine accelerates skin wound healing

2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Repair ◽  
Healing Process ◽  
Topical Administration ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

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.

Myostatin-null mice exhibit delayed skin wound healing through the blockade of transforming growth factor-β signaling by decorin

2012 ◽  
Vol 302 (8) ◽  
pp. C1213-C1225 ◽  
Author(s):  
Chen Zhang ◽  
Chek Kun Tan ◽  
Craig McFarlane ◽  
Mridula Sharma ◽  
Nguan Soon Tan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Myostatin (Mstn) is a secreted growth and differentiation factor that belongs to the transforming growth factor-β (TGF-β) superfamily. Mstn has been well characterized as a regulator of myogenesis and has been shown to play a critical role in postnatal muscle regeneration. Herein, we report for the first time that Mstn is expressed in both epidermis and dermis of murine and human skin and that Mstn-null mice exhibited delayed skin wound healing attributable to a combination of effects resulting from delayed epidermal reepithelialization and dermal contraction. In epidermis, reduced keratinocyte migration and protracted keratinocyte proliferation were observed, which subsequently led to delayed recovery of epidermal thickness and slower reepithelialization. Furthermore, primary keratinocytes derived from Mstn-null mice displayed reduced migration capacity and increased proliferation rate as assessed through in vitro migration and adhesion assays, as well as bromodeoxyuridine incorporation and Western blot analysis. Moreover, in dermis, both fibroblast-to-myofibroblast transformation and collagen deposition were concomitantly reduced, resulting in a delayed dermal wound contraction. These decreases are due to the inhibition of TGF-β signaling. In agreement, the expression of decorin, a naturally occurring TGF-β suppressor, was elevated in Mstn-null mice; moreover, topical treatment with TGF-β1 protein rescued the impaired skin wound healing observed in Mstn-null mice. These observations highlight the interplay between TGF-β and Mstn signaling pathways, specifically through Mstn regulation of decorin levels during the skin wound healing process. Thus we propose that Mstn agonists might be beneficial for skin wound repair.

scholarly journals Stem Cell-Derived Nanovesicles: A Novel Cell-Free Therapy for Wound Healing

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jianghong Huang ◽  
Jun Zhang ◽  
Jianyi Xiong ◽  
Shuqing Sun ◽  
Jiang Xia ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stem Cell ◽  
Wound Repair ◽  
Current Knowledge ◽  
Healing Process ◽  
Biologically Active ◽  
Research Progress ◽  
Wound Healing Process ◽  
Messenger Rnas ◽  
Skin Wound Healing

Wound healing and regeneration are a dynamic and complex process that requires a collaborative effort between growth factors, epidermal cells, dermal cells, extracellular matrix, and vessels local to the wound area. Mesenchymal stem cells participate in the recruitment site, mainly by releasing secretory factors and matrix proteins to promote wound healing. Stem cell-derived nanovesicles (CDNs), including microvesicles, exosomes, and exosome mimetics, contain most of the biologically active substances of their parent cells and have similar effects. CDNs can shuttle various proteins, messenger RNAs, and microRNAs to regulate the activity of receptor cells, and they play important roles in skin wound healing. This article reviews recent research progress on CDNs for wound repair. We summarize current knowledge on how CDNs regulate immunity, fibroblast activity, angiogenesis, and scar formation in the wound healing process. This review can help researchers explore new treatment strategies to enhance the therapeutic efficacy of CDNs, which have a promising future as naturally cell-free therapies.

scholarly journals The Role of MSC in Wound Healing, Scarring and Regeneration

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1729
Author(s):  
Raquel Guillamat-Prats
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Therapeutic Potential ◽  
Healing Process ◽  
Repair Process ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Matrix Remodeling ◽  
Skin Wound Healing ◽  
Tissue Repair And Regeneration

Tissue repair and regeneration after damage is not completely understood, and current therapies to support this process are limited. The wound healing process is associated with cell migration and proliferation, extracellular matrix remodeling, angiogenesis and re-epithelialization. In normal conditions, a wound will lead to healing, resulting in reparation of the tissue. Several risk factors, chronic inflammation, and some diseases lead to a deficient wound closure, producing a scar that can finish with a pathological fibrosis. Mesenchymal stem/stromal cells (MSCs) are widely used for their regenerative capacity and their possible therapeutically potential. Derived products of MSCs, such as exosomes or extravesicles, have shown a therapeutic potential similar to MSCs, and these cell-free products may be interesting in clinics. MSCs or their derivative products have shown paracrine beneficial effects, regulating inflammation, modifying the fibroblast activation and production of collagen and promoting neovascularization and re-epithelialization. This review describes the effects of MSCs and their derived products in each step of the wound repair process. As well, it reviews the pre-clinical and clinical use of MSCs to benefit in skin wound healing in diabetic associated wounds and in pathophysiological fibrosis.

scholarly journals Systemic and topical administration of spermidine accelerates skin wound healing

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Repair ◽  
Healing Process ◽  
Topical Administration ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

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.

scholarly journals Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 735 ◽  
Author(s):  
Erika Maria Tottoli ◽  
Rossella Dorati ◽  
Ida Genta ◽  
Enrica Chiesa ◽  
Silvia Pisani ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Healing Process ◽  
Skin Wound ◽  
Skin Regeneration ◽  
Bioactive Molecules ◽  
Wound Healing Process ◽  
Skin Wound Healing

Skin wound healing shows an extraordinary cellular function mechanism, unique in nature and involving the interaction of several cells, growth factors and cytokines. Physiological wound healing restores tissue integrity, but in many cases the process is limited to wound repair. Ongoing studies aim to obtain more effective wound therapies with the intention of reducing inpatient costs, providing long-term relief and effective scar healing. The main goal of this comprehensive review is to focus on the progress in wound medication and how it has evolved over the years. The main complications related to the healing process and the clinical management of chronic wounds are described in the review. Moreover, advanced treatment strategies for skin regeneration and experimental techniques for cellular engineering and skin tissue engineering are addressed. Emerging skin regeneration techniques involving scaffolds activated with growth factors, bioactive molecules and genetically modified cells are exploited to overcome wound healing technology limitations and to implement personalized therapy design.

scholarly journals Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2554
Author(s):  
Marek Konop ◽  
Anna K. Laskowska ◽  
Mateusz Rybka ◽  
Ewa Kłodzińska ◽  
Dorota Sulejczak ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Healing Process ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Diabetic Mice ◽  
Full Thickness ◽  
Skin Wound Healing ◽  
Impaired Wound Healing

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

scholarly journals Topical Saudi Arabia Talh honey (Acacia nilotica) on surgical wound healing activity

2020 ◽  
Author(s):  
Ahmed G. Hegazi ◽  
Faiz M. Al Guthami ◽  
Mohamed H. Basiouny ◽  
Ahmed F.M. Al Gethami
Keyword(s):  
Wound Healing ◽  
Saudi Arabia ◽  
Wound Repair ◽  
Healing Process ◽  
Bacterial Count ◽  
Tissue Growth ◽  
Acacia Nilotica ◽  
Total Bacterial Count ◽  
Wound Healing Process ◽  
Ifn Γ

Honey has been documented as the oldest traditional medicine. It has been effective in suppressing inflammation, wound repair enhancer, and rapid autolytic debridement. The aim of this investigation was to evaluate the role of Saudi Arabia Talh honey (Acacia nilotica) dressing as a good alternative in care of diabetic foot (DFU) healing activity for twenty patients, wound total bacterial count, and serum cytokines levels (IFN-γ, IL-1, and IL-6). The results showed that Talh honey stimulates the wound healing process, broad-spectrum antibacterial activity, and reduction in the proinflammatory cytokines IFN-γ, IL-1, and IL-6 levels. It could be concluded that Talh honey bioactivities enhance wound healing by promoting tissue growth leading to wound repair, antibacterial, and reduction of inflammation.

scholarly journals Expression of VEGF and TGF-β Genes in Skin Wound Healing Process Induced Using Phenytoin in Male Rats

2019 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Roghaye Savari ◽  
Mohammad Shafiei ◽  
Hamid Galehdari ◽  
Mahnaz Kesmati
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Skin Wound ◽  
Male Rats ◽  
Wound Healing Process ◽  
Skin Wound Healing

P2Y2R activation by nucleotides promotes skin wound-healing process

2014 ◽  
Vol 23 (7) ◽  
pp. 480-485 ◽  
Author(s):  
Hana Jin ◽  
Jihye Seo ◽  
So Young Eun ◽  
Young Nak Joo ◽  
Sang Won Park ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing
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