222. A new role for activin in endometrial restoration after menses

2008 ◽  
Vol 20 (9) ◽  
pp. 22
Author(s):  
T. J. Kaitu'u-Lino ◽  
D. J. Phillips ◽  
N. B. Morison ◽  
L. A. Salamonsen
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Abnormal Uterine Bleeding ◽  
Positive Control ◽  
Activin A ◽  
In Vivo Studies ◽  
Skin Wound Healing ◽  
Complete Repair

10% of Australian women suffer from abnormal uterine bleeding (AUB). To stop endometrial bleeding after menstruation, the endometrium must repair adequately. We propose that endometrial restoration after menstruation has characteristics of wound healing and that inadequate endometrial repair may result in AUB. In vivo studies support a contribution of activins to skin wound healing: in mice overexpressing activins' natural inhibitor, follistatin, wound healing is significantly delayed (1). We hypothesised that activin would enhance endometrial repair and examined its contribution using an in vitro wound healing model and our well characterised in vivo mouse model of endometrial breakdown and repair (2). For the in vitro model, confluent human endometrial epithelial cells (ECC-1 cell line) were wounded and treated with carrier protein (control, 0.1% BSA), activin A (50ng/mL) or EGF (positive control: 50ng/mL). Wound areas were quantitated daily for 6 days. For the in vivo study, serum follistatin levels were measured by ELISA in follistatin overexpressing mice (FS) (2) and wild-type (WT) littermates. Mice were induced to undergo endometrial breakdown and repair (mimicking menstruation in women). Activin βA was immunolocalised during endometrial repair, and extent of repair assessed using our morphological scoring system (2). ECC-1 wound repair was significantly (P < 0.05) enhanced by activin A treatment v. control from days 2–6 of culture. In WT mice, activin βA localised to areas of endometrial repair. Serum follistatin was significantly elevated in FS mice v. controls (33.3 ± 3.8 v 7.07 ± 1.8 ng/mL, P < 0.01). In FS mice (n = 8) only 50% of uterine sections showed complete repair after endometrial breakdown, significantly less than those from WT animals (n = 15, P < 0.05) where 85% of sections demonstrated complete repair. These results demonstrate for the first time that activin A functions to promote endometrial restoration following menses and that this can be delayed under physiological conditions: such studies indicate potential treatments for AUB. (1) Wankell et al. (2001) EMBO J 20:5361–5372 (2) Kaitu'u-Lino et al. (2007) Endocrinology 148:5105–5111

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.

scholarly journals Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

2020 ◽  
Vol 8 ◽  
Author(s):  
Pengcheng Xu ◽  
Yaguang Wu ◽  
Lina Zhou ◽  
Zengjun Yang ◽  
Xiaorong Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Platelet Rich Plasma ◽  
Skin Wound ◽  
Local Inflammation ◽  
Skin Wound Healing

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.

scholarly journals Bioinspired mechanically active adhesive dressings to accelerate wound closure

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw3963 ◽  
Author(s):  
S. O. Blacklow ◽  
J. Li ◽  
B. R. Freedman ◽  
M. Zeidi ◽  
C. Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Healing Process ◽  
Skin Wound ◽  
Wound Management ◽  
In Vivo Studies ◽  
Skin Wound Healing ◽  
Accelerate Wound Healing

Inspired by embryonic wound closure, we present mechanically active dressings to accelerate wound healing. Conventional dressings passively aid healing by maintaining moisture at wound sites. Recent developments have focused on drug and cell delivery to drive a healing process, but these methods are often complicated by drug side effects, sophisticated fabrication, and high cost. Here, we present novel active adhesive dressings consisting of thermoresponsive tough adhesive hydrogels that combine high stretchability, toughness, tissue adhesion, and antimicrobial function. They adhere strongly to the skin and actively contract wounds, in response to exposure to the skin temperature. In vitro and in vivo studies demonstrate their efficacy in accelerating and supporting skin wound healing. Finite element models validate and refine the wound contraction process enabled by these active adhesive dressings. This mechanobiological approach opens new avenues for wound management and may find broad utility in applications ranging from regenerative medicine to soft robotics.

scholarly journals Natural-Based Biomaterial for Skin Wound Healing (Gelatin vs. Collagen): Expert Review

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2319
Author(s):  
Ruth Naomi ◽  
Hasnah Bahari ◽  
Pauzi Muhd Ridzuan ◽  
Fezah Othman
Keyword(s):  
Wound Healing ◽  
Biological Activities ◽  
Biological Effects ◽  
Skin Wound ◽  
In Vivo Studies ◽  
Skin Wound Healing ◽  
Vast Number ◽  
Expert Review

Collagen (Col) and gelatin are most extensively used in various fields, particularly in pharmaceuticals and therapeutics. Numerous researchers have proven that they are highly biocompatible to human tissues, exhibit low antigenicity and are easy to degrade. Despite their different sources both Col and gelatin have almost the same effects when it comes to wound healing mechanisms. Considering this, the bioactivity and biological effects of both Col and gelatin have been, and are being, constantly investigated through in vitro and in vivo assays to obtain maximum outcomes in the future. With regard to their proven nutritional values as sources of protein, Col and gelatin products exert various possible biological activities on cells in the extracellular matrix (ECM). In addition, a vast number of novel Col and gelatin applications have been discovered. This review compared Col and gelatin in terms of their structures, sources of derivatives, physicochemical properties, results of in vitro and in vivo studies, their roles in wound healing and the current challenges in wound healing. Thus, this review provides the current insights and the latest discoveries on both Col and gelatin in their wound healing mechanisms.

scholarly journals Discovery and Characterization of a High-Affinity Small Peptide Ligand, H1, Targeting FGFR2IIIc for Skin Wound Healing

2018 ◽  
Vol 49 (3) ◽  
pp. 1074-1089 ◽  
Author(s):  
Ying Zhao ◽  
Qiang Wang ◽  
Yuan Jin ◽  
Yadan Li ◽  
Changjun Nie ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Chorioallantoic Membrane ◽  
Skin Wound ◽  
Small Peptide ◽  
Skin Wound Healing ◽  
Wound Model

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.

scholarly journals Regenerative Skin Wound Healing in Mammals: State-of-the-Art on Growth Factor and Stem Cell Based Treatments

2015 ◽  
Vol 36 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Bizunesh M. Borena ◽  
Ann Martens ◽  
Sarah Y. Broeckx ◽  
Evelyne Meyer ◽  
Koen Chiers ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stem Cell ◽  
Growth Factor ◽  
Wound Repair ◽  
Cell Types ◽  
Skin Wound ◽  
Wound Management ◽  
Skin Wound Healing

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.

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.

The Anti-tumor Activity and Mechanisms of rLj-RGD3 on Human Laryngeal Squamous Carcinoma Hep2 Cells

2020 ◽  
Vol 19 (17) ◽  
pp. 2108-2119
Author(s):  
Yang Jin ◽  
Li Lv ◽  
Shu-Xiang Ning ◽  
Ji-Hong Wang ◽  
Rong Xiao
Keyword(s):  
Wound Healing ◽  
Western Blot ◽  
Morphological Changes ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Tunel Staining ◽  
Dna Ladder ◽  
Western Blot Assay

Background: Laryngeal Squamous Cell Carcinoma (LSCC) is a malignant epithelial tumor with poor prognosis and its incidence rate increased recently. rLj-RGD3, a recombinant protein cloned from the buccal gland of Lampetra japonica, contains three RGD motifs that could bind to integrins on the tumor cells. Methods: MTT assay was used to detect the inhibitory rate of viability. Giemsa’s staining assay was used to observe the morphological changes of cells. Hoechst 33258 and TUNEL staining assay, DNA ladder assay were used to examine the apoptotic. Western blot assay was applied to detect the change of the integrin signal pathway. Wound-healing assay, migration, and invasion assay were used to detect the mobility of Hep2 cells. H&E staining assay was used to show the arrangement of the Hep2 cells in the solid tumor tissues. Results: In the present study, rLj-RGD3 was shown to inhibit the viability of LSCC Hep2 cells in vitro by inducing apoptosis with an IC50 of 1.23µM. Western blot showed that the apoptosis of Hep2 cells induced by rLj- RGD3 was dependent on the integrin-FAK-Akt pathway. Wound healing, transwells, and western blot assays in vitro showed that rLj-RGD3 suppressed the migration and invasion of Hep2 cells by integrin-FAKpaxillin/ PLC pathway which could also affect the cytoskeleton arrangement in Hep2 cells. In in vivo studies, rLj-RGD3 inhibited the growth, tumor volume, and weight, as well as disturbed the tissue structure of the solid tumors in xenograft models of BALB/c nude mice without reducing their body weights. Conclusion: hese results suggested that rLj-RGD3 is an effective and safe suppressor on the growth and metastasis of LSCC Hep2 cells from both in vitro and in vivo experiments. rLj-RGD3 might be expected to become a novel anti-tumor drug to treat LSCC patients in the near future.

scholarly journals Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Closure ◽  
Expression Patterns ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Specific Expression ◽  
Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

Sign in / Sign up

Export Citation Format

Share Document