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 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 Migration and Proliferation Effects of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) and Thymoquinone (TQ) on In Vitro Wound Healing Models

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Henna Roshini Alexander ◽  
Sharifah Sakinah Syed Alwi ◽  
Latifah Saiful Yazan ◽  
Fatin Hanani Zakarial Ansar ◽  
Yong Sze Ong
Keyword(s):  
Wound Healing ◽  
Nigella Sativa ◽  
Drug Carrier ◽  
Healing Process ◽  
Diabetic Patients ◽  
Nanostructured Lipid Carrier ◽  
Impaired Wound Healing ◽  
And Migration ◽  
Proliferation And Migration

Wound healing is a regulated biological event that involves several processes including infiltrating leukocyte subtypes and resident cells. Impaired wound healing is one of the major problems in diabetic patients due to the abnormal physiological changes of tissues and cells in major processes. Thymoquinone, a bioactive compound found in Nigella sativa has been demonstrated to possess antidiabetic, anti-inflammatory, and antioxidant effects. Today, the rapidly progressing nanotechnology sets a new alternative carrier to enhance and favour the speed of healing process. In order to overcome its low bioavailability, TQ is loaded into a colloidal drug carrier known as a nanostructured lipid carrier (NLC). This study aimed to determine the effect of TQ-NLC and TQ on cell proliferation and migration, mode of cell death, and the antioxidant levels in normal and diabetic cell models, 3T3 and 3T3-L1. Cytotoxicity of TQ-NLC and TQ was determined by MTT assay. The IC10 values obtained for 3T3-L1 treated with TQ-NLC and TQ for 24 hours were 4.7 ± 3.3 and 5.3 ± 0.6 μM, respectively. As for 3T3, the IC10 values obtained for TQ-NLC and TQ at 24 hours were 4.3 ± 0.17 and 3.9 ± 2.05 μM, respectively. TQ-NLC was observed to increase the number of 3T3 and 3T3-L1 healthy cells (87–95%) and gradually decrease early apoptotic cells in time- and dose-dependant manner compared with TQ. In the proliferation and migration assay, 3T3-L1 treated with TQ-NLC showed higher proliferation and migration rate (p<0.05) compared with TQ. TQ-NLC also acted as an antioxidant by reducing the ROS levels in both cells after injury at concentration as low as 3 μM. Thus, this study demonstrated that TQ-NLC has better proliferation and migration as well as antioxidant effect compared with TQ especially on 3T3-L1 which confirms its ability as a good antidiabetic and antioxidant agent.

Inherent differences in morphology, proliferation, and migration in saphenous vein smooth muscle cells cultured from nondiabetic and Type 2 diabetic patients

2009 ◽  
Vol 297 (5) ◽  
pp. C1307-C1317 ◽  
Author(s):  
Haifa A. Madi ◽  
Kirsten Riches ◽  
Philip Warburton ◽  
David J. O'Regan ◽  
Neil A. Turner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Saphenous Vein ◽  
Glucose Concentration ◽  
Cell Counting ◽  
Diabetic Patients ◽  
Graft Stenosis ◽  
Increased Risk ◽  
And Migration ◽  
Proliferation And Migration

Individuals with Type 2 diabetes mellitus (T2DM) are at increased risk of saphenous vein (SV) graft stenosis following coronary artery bypass. Graft stenosis is caused by intimal hyperplasia, a pathology characterized by smooth muscle cell (SMC) proliferation and migration. We hypothesized that SV-SMC from T2DM patients were intrinsically more proliferative and migratory than those from nondiabetic individuals. SV-SMC were cultured from nondiabetic and T2DM patients. Cell morphology (light microscopy, immunocytochemistry), S100A4 expression (real-time RT-PCR, immunoblotting), proliferation (cell counting), migration (Boyden chamber assay), and cell signaling (immunoblotting with phosphorylation state-specific antibodies) were studied. SV-SMC from T2DM patients were morphologically distinct from nondiabetic patients and exhibited a predominantly rhomboid phenotype, accompanied by disrupted F-actin cytoskeleton, disorganized α-smooth muscle actin network, and increased focal adhesion formation. However, no differences were observed in expression of the calcium-binding protein S100A4, a marker of rhomboid SMC phenotype, between the two cell populations. T2DM cells were less proliferative in response to fetal calf serum than nondiabetic cells, but both populations had similar proliferative responses to insulin plus PDGF. Under high glucose concentration conditions in the presence of insulin, migration of diabetic SV-SMC was greater than nondiabetic cells. Glucose concentration did not affect SV-SMC proliferation. No differences in insulin or PDGF-induced phosphorylation of ERK-1/2 or components of the Akt pathway (Akt-Ser473, Akt-Thr308, and GSK-3β) were apparent between the two populations. In conclusion, SV-SMC from T2DM patients differ from nondiabetic SV-SMC in that they exhibit a rhomboid phenotype and are more migratory, but less proliferative, in response to serum.

scholarly journals The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yi Cao ◽  
Li Xu ◽  
Xiaohong Yang ◽  
Yuan Dong ◽  
Hongbin Luo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Cell Counting ◽  
Migration Ability ◽  
Cell Growth And Migration ◽  
Cell Based Therapy ◽  
And Migration ◽  
Proliferation And Migration

Background. Refractory wound healing is a severe complication of diabetes with a significant socioeconomic burden. Whereas current therapies are insufficient to accelerate repair, stem cell-based therapy is increasingly recognized as an alternative that improves healing outcomes. The aim of the present study is to explore the role of cycloastragenol (CAG), a naturally occurring compound in Astragali Radix, in ameliorating refractory cutaneous wound healing in vitro, which may provide a new insight into therapeutic strategy for diabetic wounds. Methods. Human epidermal stem cells (EpSCs) obtained from nine patients were exposed to CAG, with or without DKK1 (a Wnt signaling inhibitor). A lentiviral short hairpin RNA (shRNA) system was used to establish the telomerase reverse transcriptase (TERT) and β-catenin knockdown cell line. Cell counting kit-8, scratch wound healing, and transwell migration assay were used to determine the effects of CAG in cell growth and migration. The activation of TERT, β-catenin, and c-Myc was determined using real-time qPCR and western blot analysis. Chromatin immunoprecipitation (ChIP) was performed to evaluate the associations among CAG, TERT, and Wnt/β-catenin signals. Results. CAG not only promoted the proliferation and migration ability of EpSCs but also increased the expression levels of TERT, β-catenin, c-Myc. These effects of CAG were most pronounced at a dose of 0.3 μM. Notably, the CAG-promoted proliferative and migratory abilities of EpSCs were abrogated in TERT and β-catenin-silenced cells. In addition, the ChIP results strongly suggested that CAG-modulated TERT was closely associated with the activation of Wnt/β-catenin signaling. Conclusion. Our data indicate that CAG is a TERT activator of EpSCs and is associated with their proliferation and migration, a role it may play through the activation of Wnt/β-catenin signaling.

scholarly journals Reactive oxygen species and bacterial biofilms in diabetic wound healing

2016 ◽  
Vol 48 (12) ◽  
pp. 889-896 ◽  
Author(s):  
Aksone Nouvong ◽  
Aaron M. Ambrus ◽  
Ellen R. Zhang ◽  
Lucas Hultman ◽  
Hilary A. Coller
Keyword(s):  
Reactive Oxygen Species ◽  
Wound Healing ◽  
Mouse Models ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Reactive Oxygen ◽  
Bacterial Biofilms ◽  
Diabetic Patients ◽  
Oxygen Species ◽  
Early Phases

Chronic wounds are a common and debilitating complication for the diabetic population. It is challenging to study the development of chronic wounds in human patients; by the time it is clear that a wound is chronic, the early phases of wound healing have passed and can no longer be studied. Because of this limitation, mouse models have been employed to better understand the early phases of chronic wound formation. In the past few years, a series of reports have highlighted the importance of reactive oxygen species and bacterial biofilms in the development of chronic wounds in diabetics. We review these recent findings and discuss mouse models that are being utilized to enhance our understanding of these potentially important contributors to chronic wound formation in diabetic patients.

scholarly journals Conjugation of CTGF with Reduced Graphene Oxide Nanoparticles for the Development of Wound Healing Hydrogel Patch

2020 ◽  
Author(s):  
Raza ur Rehman Syed ◽  
Robin augustine ◽  
Alap ali Zahid ◽  
Anwarul Hasan
Keyword(s):  
Wound Healing ◽  
Graphene Oxide ◽  
Reduced Graphene Oxide ◽  
Chronic Wounds ◽  
Healing Process ◽  
Wound Healing Process ◽  
Reduced Graphene ◽  
And Migration ◽  
Migration Of Cells ◽  
Proliferation And Migration

Non-healing chronic wounds are the key concern in type-2 diabetes that frequently leads to chronic infections, finally causing amputation of limbs, organs etc. Decrease in the proliferation and migration of cells such as keratinocytes and fibroblasts is the major reason for the development of such chronic diabetic wounds. Multiple evidences have shown that CTGF and reduced graphene oxide possesses angiogenic property and promote wound healing by promoting proliferation and migration of fibroblasts and keratinocytes cells.Conjugation of rGO with CTGF using EDC-NHS chemistry is a novel approach to accelerate the wound healing process. In the current work, we have developed a rGO/CTGF incorporated GelMA hydrogel dressing to improve wound healing by increasing proliferation and migration of cells as well as promoting formation of new blood vessels for increased supply of nutrients, oxygen and growth factors to wound area

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.

Abstract 68: Endostatin Promotes Proliferation and Migration of Rat Myofibroblasts Isolated From the Infarcted Area After Myocardial Infarction

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Muneyoshi Okada ◽  
Yuka Hirano ◽  
Hideyuki Yamawaki
Keyword(s):  
Myocardial Infarction ◽  
Type I Collagen ◽  
Left Ventricular ◽  
Angiogenic Factor ◽  
Cell Counting ◽  
Boyden Chamber ◽  
Type I ◽  
A Cell ◽  
And Migration ◽  
Proliferation And Migration

Background: Endostatin, a 20 kDa non-collagenous fragment of type XVIII collagen, is known as an endogenous anti-angiogenic factor. In the heart tissues of experimental heart failure models, such as cardiac hypertrophy and myocardial infarction, the expression levels of endostatin increase. Proliferation, migration and collagen synthesis of myofibroblasts are important processes during the tissue remodeling in injury sites after myocardial infarction. However, the effects of endostatin on cardiac myofibroblasts have not been clarified. We investigated the effect of endostatin on the functions of myofibroblasts isolated from infarcted myocardial tissues of rat. Methods and Results: Left ventricular myocardial infarction was induced by ligation the left anterior descending coronary artery of male Wistar rats. The infarcted myocardial tissues were harvested 2 weeks after the operation and placed on the culture plate with serum-containing medium. Migrated cells from the tissues were isolated and used as myofibroblasts. High expression of α-smooth muscle actin, vimentin and type I collagen in these cells were confirmed by immunofluorescence staining. Cell counting assay was performed to determine a cell proliferation. Endostatin (100-3000 ng/ml, 48 h) increased the proliferation of myofibroblasts. Boyden chamber assay was performed to measure a cell migration. Endostatin (300-3000 ng/ml, 24 h) stimulated the migration of myofibroblasts. Western blotting was performed to measure a secretion of type I collagen. Endostatin (100-3000 ng/ml, 24 h) had no influence on it. Conclusions: These data suggest that endostatin might promote scar formation after myocardial infarction through the activation of proliferation and migration of myofibroblasts.

scholarly journals RUNX1 can mediate the glucose and O-GlcNAc-driven proliferation and migration of human retinal microvascular endothelial cells

2021 ◽  
Vol 9 (1) ◽  
pp. e001898
Author(s):  
Xindan Xing ◽  
Hanying Wang ◽  
Tian Niu ◽  
Yan Jiang ◽  
Xin Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Tube Formation ◽  
Cell Counting ◽  
Microvascular Endothelial Cells ◽  
High Glucose Condition ◽  
Microvascular Endothelial ◽  
And Migration ◽  
Glucose Condition ◽  
Proliferation And Migration

IntroductionThis study aims to determine whether high glucose condition and dynamic O-linked N-acetylglucosamine (O-GlcNAc) modification can promote the proliferation and migration of human retinal microvascular endothelial cells (HRMECs) and whether Runt-related transcription factor 1 (RUNX1) could mediate the glucose and O-GlcNAc-driven proliferation and migration of HRMECs.Research design and methodsWestern blot analysis was used to detect the O-GlcNAc modification level and RUNX1 level in cells and retina tissues, cell growth was studied by cell counting kit-8 assay, cell proliferation was detected by immunofluorescence staining. Then, cell migration and tube formation were investigated by scratch-wound assay, Transwell assay, and tube-forming assay. The changes of retinal structure were detected by H&E staining. The O-GlcNAc modification of RUNX1 was detected by immunoprecipitation.ResultsHigh glucose increases pan-cellular O-GlcNAc modification and the proliferation and migration of HRMECs. Hence, O-GlcNAc modification is critical for the proliferation and migration of HRMECs. RUNX1 mediates the glucose and O-GlcNAc-driven proliferation and migration in HRMECs. RUNX1 can be modified by O-GlcNAc, and that the modification is enhanced in a high glucose environment.ConclusionsThe present study reveals that high glucose condition directly affects retinal endothelial cells (EC) function, and O-GlcNAc modification is critical for the proliferation and migration of HRMECs, RUNX1 may take part in this mechanism, and maybe the function of RUNX1 is related to its O-GlcNAc modification level, which provides a new perspective for studying the mechanism of RUNX1 in diabetic retinopathy.

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.

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