scholarly journals Defining stem cell dynamics and migration during wound healing in mouse skin epidermis

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Mariaceleste Aragona ◽  
Sophie Dekoninck ◽  
Steffen Rulands ◽  
Sandrine Lenglez ◽  
Guilhem Mascré ◽  
...  
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wound ◽  
Mouse Skin ◽  
Molecular Profiling ◽  
Clonal Analysis ◽  
Lineage Tracing ◽  
Cell Dynamics ◽  
And Migration ◽  
Skin Epidermis

Abstract Wound healing is essential to repair the skin after injury. In the epidermis, distinct stem cells (SCs) populations contribute to wound healing. However, how SCs balance proliferation, differentiation and migration to repair a wound remains poorly understood. Here, we show the cellular and molecular mechanisms that regulate wound healing in mouse tail epidermis. Using a combination of proliferation kinetics experiments and molecular profiling, we identify the gene signatures associated with proliferation, differentiation and migration in different regions surrounding the wound. Functional experiments show that SC proliferation, migration and differentiation can be uncoupled during wound healing. Lineage tracing and quantitative clonal analysis reveal that, following wounding, progenitors divide more rapidly, but conserve their homoeostatic mode of division, leading to their rapid depletion, whereas SCs become active, giving rise to new progenitors that expand and repair the wound. These results have important implications for tissue regeneration, acute and chronic wound disorders.

scholarly journals PTH Derivative Promotes Chronic Wound Healing via Synergistic Multicellular Stimulating and Exosomal Activities

2019 ◽  
Author(s):  
Yi-Fan Shen ◽  
Jing-Huan Huang ◽  
Kai-Yang Wang ◽  
Jin Zheng ◽  
Lin Cai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Intercellular Communication ◽  
Indirect Effects ◽  
Chronic Wound ◽  
Therapeutic Effects ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Chronic diabetic wounds are a disturbing and rapidly growing clinical problem. Parathyroid hormone related peptide (PTHrP-2) was assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in chronic wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 was determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 was determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos was added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played hub role in PTHrP-2 indirect effects in wound healing. Conclusion: The findings of this study indicate that PTHrP-2, a multifunctional factor, can promote chronic wound healing via synergistic multicellular stimulating and exosomal activities.

scholarly journals Vaccarin Regulates Diabetic Chronic Wound Healing through FOXP2/AGGF1 Pathways

2020 ◽  
Vol 21 (6) ◽  
pp. 1966
Author(s):  
Yixiao Liu ◽  
Jiangnan Sun ◽  
Xinyu Ma ◽  
Shuangshuang Li ◽  
Min Ai ◽  
...  
Keyword(s):  
Wound Healing ◽  
High Glucose ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Angiogenic Factor ◽  
Cell Counting ◽  
Sensory Loss ◽  
Diabetic Patients ◽  
And Migration ◽  
Proliferation And Migration

Background: Diabetes mellitus is a growing global health issue nearly across the world. Diabetic patients who are prone to develop diabetes-related complications often exhibit progressive neuropathy (painless and sensory loss). It is usual for small wounds to progress to ulceration, which especially worsens with peripheral arterial disease and in the presence of anaerobic bacteria, culminating into gangrene. In our study, vaccarin (VAC), the main active monomer extracted from Chinese herb vaccariae semen, is proven to have a role in promoting diabetic chronic wound healing through a cytoprotective role under high glucose conditions. Materials and methods: We constructed a pressure ulcer on both VAC-treated and control mice based on a type 1 diabetes (T1DM) model. The wound healing index was evaluated by an experimental wound assessment tool (EWAT). We also determined the effect of VAC on the proliferation and cell migration of human microvascular endothelial cells (HMEC-1) by a cell counting kit (CCK-8), a scratch and transwell assay. Results: The results demonstrated that VAC could promote the proliferation and migration of high glucose-stimulated HMEC-1 cells, which depend on the activation of FOXP2/AGGF1. Activation of the angiogenic factor with G patch and FHA domains 1 (AGGF1) caused enhanced phosphorylation of serine/threonine kinase (Akt) and extracellular regulated protein kinases (Erk1/2). By silencing the expression of forkhead box p2 (FOXP2) protein by siRNA, both mRNA and protein expression of AGGF1 were downregulated, leading to a decreased proliferation and migration of HMEC-1 cells. In addition, a diabetic chronic wound model in vivo unveiled that VAC had a positive effect on chronic wound healing, which involved the activation of the above-mentioned pathways. Conclusions: In summary, our study found that VAC promoted chronic wound healing in T1DM mice by activating the FOXP2/AGGF1 pathway, indicating that VAC may be a promising candidate for the treatment of the chronic wounds of diabetic patients.

scholarly journals Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice

2017 ◽  
Vol 8 (6) ◽  
pp. e2845-e2845 ◽  
Author(s):  
Eric Press ◽  
Katanya C Alaga ◽  
Kevin Barr ◽  
Qing Shao ◽  
Felicitas Bosen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Skin Diseases ◽  
Mouse Skin ◽  
Skin Wound ◽  
Keratinocyte Differentiation ◽  
Gap Junctional Intercellular Communication ◽  
Elevated Expression ◽  
And Migration ◽  
Foot Pad

Abstract Several mutant mice have been generated to model connexin (Cx)-linked skin diseases; however, the role of connexins in skin maintenance and during wound healing remains to be fully elucidated. Here we generated a novel, viable, and fertile mouse (Cx26CK14-S17F/+) with the keratitis-ichthyosis-deafness mutant (Cx26S17F) driven by the cytokeratin 14 promoter. This mutant mouse mirrors several Cx26-linked human skin pathologies suggesting that the etiology of Cx26-linked skin disease indeed stems from epidermal expression of the Cx26 mutant. Cx26CK14-S17F/+ foot pad epidermis formed severe palmoplantar keratoderma, which expressed elevated levels of Cx26 and filaggrin. Primary keratinocytes isolated from Cx26CK14-S17F/+ neonates exhibited reduced gap junctional intercellular communication and migration. Furthermore, Cx26CK14-S17F/+ mouse skin wound closure was normal but repaired epidermis appeared hyperplastic with elevated expression of cytokeratin 6. Taken together, we suggest that the Cx26S17F mutant disturbs keratinocyte differentiation and epidermal remodeling following wound closure. We further posit that Cx26 contributes to epidermal homeostasis by regulating keratinocyte differentiation, and that mice harboring a disease-linked Cx26 mutant display epidermal abnormalities yet retain most wound healing properties.

scholarly journals Mechanism of resistin-induced enhancement of proliferation and migration of ovarian cancer cells

2020 ◽  
Author(s):  
Li Pang ◽  
Xian-li Li
Keyword(s):  
Ovarian Cancer ◽  
Wound Healing ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Ovarian Epithelial Carcinoma ◽  
And Migration ◽  
Proliferation And Migration

IntroductionResistin, a novel hormone secreted by human adipocytes and mononuclear cells, is associated with obesity, insulin resistance, and inflammation. Recent studies showed that resistin plays a key role in ovarian cancer cells. In this study, we investigated the potential of resistin to regulate the proliferation and migration of ovarian cancer cells.Material and methodsA series of in vitro functional experiments were carried out to elucidate the role of resistin in ovarian cancer progression and the molecular mechanisms underlying its role.ResultsResistin enhanced the proliferation of human ovarian epithelial carcinoma cells (HO-8910) in a time- and dose-dependent manner (30–100 ng/ml). Furthermore, HO-8910 cells cultured in adipocyte-conditioned medium showed dramatically increased rates of proliferation. Resistin knockout during adipocyte culture attenuated the proliferation of HO-8910 cells treated with adipocyte-conditioned media, indicating that resistin may promote HO-8910 cell proliferation via the mechanistic target of a rapamycin (mTOR)-mediated signaling pathway. Resistin (30–100 ng/ml) also enhanced wound-healing rates in a time- and concentration-dependent manner. Co-culturing HO-8910 cells with adipocytes also increased the wound-healing rates. Resistin expression was inhibited by miR-124-1 transcriptional activity, and resistin-mediated HO-8910 cell migration was also regulated by miR-124-1. Furthermore, we also confirmed the role of resistin in promoting tumor growth in vivo.ConclusionsThese findings suggest that resistin may serve as an effective therapeutic target for ovarian epithelial carcinoma, especially in patients who are obese.

PTH Derivative Promotes Chronic Wound Healing via Synergistic Multicellular Stimulating and Exosomal Activities

2020 ◽  
Author(s):  
Yi-Fan Shen ◽  
Jing-Huan Huang ◽  
Kai-Yang Wang ◽  
Jin Zheng ◽  
Lin Cai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Intercellular Communication ◽  
Indirect Effects ◽  
Chronic Wound ◽  
Therapeutic Effects ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Chronic diabetic wounds are a disturbing and rapidly growing clinical problem. Parathyroid hormone related peptide (PTHrP-2) was assumed as multifunctional factor in angiogenesis, fibrogenesis and re-epithelization. This study aims to test PTHrP-2 efficiency and mechanism in chronic wound healing. Methods: Through repair phenomenon in vivo some problems were detected, and further research on their mechanisms was made. In vivo therapeutic effects of PTHrP-2 was determined by HE, Masson, microfil and immunohistochemical staining. In vitro direct effects of PTHrP-2 was determined by proliferation, migration, Vascular Endothelial Grown Factor and collagen I secretion of cells and Akt/ Erk1/2 pathway change. In vitro indirect effects of PTHrP-2 was study via exosomes. Exosomes from PTHrP-2 untreated and treated HUVECs and HFF-1 cells were insolated and identified. Exosomes were co-cultured with original cells, HUVECs or HFF-1 cells, and epithelial cells. Proliferation and migration and pathway change were observed. PTHrP-2-HUVEC-Exos was added into in vivo wound to testify its hub role in PTHrP-2 indirect effects in wound healing. Results: In vivo, PTHrP-2 exerted multifunctional pro-angiogenesis, pro-firbogenesis and re-epithelization effects. In vitro, PTHrP-2 promoted proliferation and migration of endothelial and fibroblast cells, but had no effect on epithelial cells. Therefore, we tested PTHrP-2 indirect effects via exosomes. PTHrP-2 intensified intercellular communication between endothelial cells and fibroblasts and initiated endothelial-epithelial intercellular communication. PTHrP-2-HUVEC-Exos played hub role in PTHrP-2 indirect effects in wound healing. Conclusion: The findings of this study indicate that PTHrP-2, a multifunctional factor, can promote chronic wound healing via synergistic multicellular stimulating and exosomal activities.

scholarly journals Cellular and molecular mechanisms of repair in acute and chronic wound healing

2015 ◽  
Vol 173 (2) ◽  
pp. 370-378 ◽  
Author(s):  
P. Martin ◽  
R. Nunan
Keyword(s):  
Wound Healing ◽  
Molecular Mechanisms ◽  
Chronic Wound

scholarly journals ID3015 Mesenchymal stem cells for treatment of chronic wounds: A Study with autologous transplantation of adipose-derived stem cells

2017 ◽  
Vol 4 (S) ◽  
pp. 27
Author(s):  
Han Van Dinh
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Autologous Transplantation ◽  
Adipose Derived Stem Cells ◽  
Fibroblast Proliferation ◽  
Wound Site ◽  
And Migration ◽  
Proliferation And Migration

Objective: This study was to determine the effects of adipose-derived stem cells (ADSCs) on dermal fibroblasts responses to injury including migration and proliferation in vitro. We also evaluated the autologous transplantation of ADSCs on treatment of  human chronic wounds.  Subjects and methods: The proliferation and migration of fibroblast was evaluated by co-culture ADSCs with allogenic dermal fibroblast and by the scratch assay. In clinical study, autologous ADSCs were transplanted on to chronic wounds of 25 patients, who were hospitalized into the Wound Healing Department of the National Institute of Burns from April, 2015 to June, 2016. The mean age was 56.88 ± 16.81, male/female ratio was 2.12. The autologous adipose-derived stem cells at passages 5 were transplanted on surface of wound every 3÷5 days. The wound biopsies for H&E staining and for Transmission Electron Microscope  were taken before transplantation and at day 7, day15 and day 20 of studied progress.  Results: ADSCs stimulated fibroblast proliferation and migration in wound healing assay. In clinical study, before transplantation, extracellular matrix (ECM) was destroyed. After transplantation, ADSCs strongly stimulated fibroblast proliferation and fibroblasts to produce collagen. ADSCs also promoted proliferations of epithelial cells and neovascularization at the chronic wound site.  Conclusion: Autologous ADSCs promoted the wound healing process by cell proliferation and improvement of ECM in chronic wound site.

scholarly journals Astragaloside IV Downregulates β-Catenin in Rat Keratinocytes to Counter LiCl-Induced Inhibition of Proliferation and Migration

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Fu-Lun Li ◽  
Xin Li ◽  
Yi-Fei Wang ◽  
Xiu-Li Xiao ◽  
Rong Xu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Molecular Mechanisms ◽  
Colorimetric Assay ◽  
Wnt Signaling Pathway ◽  
Nuclear Antigen ◽  
Astragaloside Iv ◽  
Inhibition Of Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Re-epithelialization is a crucial step towards wound healing. The traditional Chinese medicine,Astragalus membranaceus(Fisch) Bge, has been used for hundreds of years for many kinds of ulcerated wounds. Recent research has identified the active compound in this drug as astragaloside IV (AS-IV), but the underlying molecular mechanisms of its therapeutic action on keratinocytes remain poorly understood. In this study, we used anin vitromodel of ulcer-like wound processes, lithium chloride (LiCl)-induced cultured mouse keratinocytes, to investigate the effects of AS-IV treatment. The effects on cell proliferation were evaluated by the MTS/PMS colorimetric assay, effects on cell migration were determined by a wound-healing scratch experiment, effects on the cell cycle were analyzed by flow cytometry, and effects on protein expression were analyzed by immunoblotting and immunofluorescence. LiCl strongly inhibited cell proliferation and migration, up-regulatedβ-catenin expression, and down-regulated proliferating cell nuclear antigen (PCNA) expression. AS-IV treatment attenuat the inhibition of proliferation and migration, significantly reducing the enhancedβ-catenin expression, and recovering PCNA andβ-tubulin expression. Thus, AS-IV mediates mouse keratinocyte proliferation and migrationviaregulation of the Wnt signaling pathway. Down-regulatingβ-catenin to increase keratinocyte migration and proliferation is one mechanism by which AS-IV can promote ulcerated wound healing.

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review

2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Chemotherapy Resistance ◽  
Wnt Signaling Pathway ◽  
Therapeutic Interventions ◽  
Beta Catenin ◽  
Clinical Prognosis ◽  
Invasion And Migration ◽  
And Migration

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

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