scholarly journals Effect of continuous compressive force on the expression of RANKL, OPG, and VEGF in MC3T3-E1 and MLO-Y4 cells

2018 ◽  
Author(s):  
Yuka Yashima ◽  
Masato Kaku ◽  
Taeko Yamamoto ◽  
Jin Izumino ◽  
Haruka Kagawa ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Compressive Force ◽  
Cell Types ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Key Factors ◽  
Protein Levels ◽  
Gene And Protein Expression ◽  
Receptor Activator ◽  
Endothelial Growth Factor

AbstractOsteocytes, known to have mechano-sensory functions, influence the regulation of bone remodeling. However, the mechanism by which osteocytes regulate bone metabolism when mechanical forces are being applied is still unclear. Osteoclastogenesis is mainly regulated by receptor activator of nuclear factor kappa-B ligand (RANKL); the protein osteoprotegerin (OPG) and angiogenesis also play important roles in osteogenesis. RANKL, OPG, and vascular endothelial growth factor (VEGF) are thought to be key factors for bone metabolism. In this study, we examined the effect of a continuous compressive force (CF) on the expression of RANKL, OPG, and VEGF in osteoblastic murine osteocytes (MLO-Y4) and osteoblastic (MC3T3-E1) cells. Gene and protein expression levels of RANKL, OPG, and VEGF in MLO-Y4 and MC3T3-E1 cells were quantitatively determined by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Both cell types were also subjected to a CF of 1.0 g/cm2 for 1, 3, 6, and 12 hours. Furthermore, the effect of a stretch-activated (S-A) channel was examined by gadolinium (Gd3+) administration. The ratio of gene and protein expressions of RANKL, VEGF, and RANKL/OPG in MLO-Y4 cells were significantly higher than in MC3T3-E1 cells, while the expression of OPG was significantly lower. After CF application, both cell types showed significant increases in RANKL and VEGF expression as well as the RANKL/OPG ratio. Additionally, the upregulated gene and protein levels of these factors were reduced by Gd3+ administration.These findings suggest that osteocytes play more important roles in bone metabolism and angiogenesis than osteoblasts. Osteocytes regulate the expression of RANKL, OPG, and VEGF via the S-A channel through the response to mechanical stress.

scholarly journals Identification of novel circulating angiogenic factors in small bowel angiodysplasia: a further step towards delineating the pathophysiology and defining treatment targets

2019 ◽  
Author(s):  
Grainne Holleran ◽  
Sinead Smith ◽  
Deirdre McNamara
Keyword(s):  
Growth Factor ◽  
Small Bowel ◽  
Angiogenic Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inadequate Response ◽  
Vascular Endothelial ◽  
Key Factors ◽  
Five Factors ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor

Abstract Background: Small bowel angiodysplasia (SBA) accounts for 50% of small bowel bleeding, with a poor prognosis due to inadequate response to limited treatments. A poor understanding of the pathophysiology of the condition impedes improvements in diagnosis and treatments. We previously identified the Angiopoietin pathway to be associated with SBA, however this may be only one of many angiogenic drivers. Methods: We initially measured relative levels of 55 angiogenic factors in serum of Small Bowel Angiodysplasia (SBA) patients and non-bleeding controls. Quantitative Enzyme-linked Immunosorbent Assay (ELISA) measurements of any significant factors detected were then performed in a larger group of patients and controls. Results: Serum measurements of relative levels of 55 angiogenic factors were performed in seven SBA patients and controls and identified significant differences in five factors between groups– Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2), Tissue-Inhibitor of Metalloproteinases 1 (TIMP1), Endostatin and Platelet-derived Growth Factor-AA (PDGF-AA). We found no differences in levels of Vascular Endothelial Growth Factor (VEGF). Quantitative serum ELISA measurements of TIMP1, Endostatin and PDGF-AA were performed in 20 SBA patients and controls and showed significantly lower mean levels of TIMP1 and higher levels of Endostatin in SBA patients compared to controls, with no differences in PDGF-AA levels. Conclusions: This study confirms our previous findings, that Ang1 and Ang2 are key factors associated with SBA formation, and that VEGF is unlikely to have a key role in SBA pathophysiology. We have identified two new anti-angiogenic factors likely to be involved in SBA development, TIMP1 and Endostatin. Further assessments of circulating and tissue levels of these factors may advance the discovery of the pathophysiology of SBA and identify therapeutic targets.

scholarly journals Exploring the Intracrine Functions of VEGF-A

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 128
Author(s):  
Sophie Wiszniak ◽  
Quenten Schwarz
Keyword(s):  
Cell Growth ◽  
Molecular Mechanisms ◽  
Direct Action ◽  
Cancer Therapeutics ◽  
Cell Types ◽  
Vascular Endothelial ◽  
Signalling Molecule ◽  
Endothelial Growth Factor ◽  
Important Signalling Molecule ◽  
Vegf Signalling

Vascular endothelial growth factor A (VEGF-A or VEGF) is a highly conserved secreted signalling protein best known for its roles in vascular development and angiogenesis. Many non-endothelial roles for VEGF are now established, with the discovery that VEGF and its receptors VEGFR1 and VEGFR2 are expressed in many non-vascular cell-types, as well as various cancers. In addition to secreted VEGF binding to its receptors in the extracellular space at the cell membrane (i.e., in a paracrine or autocrine mode), intracellularly localised VEGF is emerging as an important signalling molecule regulating cell growth, survival, and metabolism. This intracellular mode of signalling has been termed “intracrine”, and refers to the direct action of a signalling molecule within the cell without being secreted. In this review, we describe examples of intracrine VEGF signalling in regulating cell growth, differentiation and survival, both in normal cell homeostasis and development, as well as in cancer. We further discuss emerging evidence for the molecular mechanisms underpinning VEGF intracrine function, as well as the implications this intracellular mode of VEGF signalling may have for use and design of anti-VEGF cancer therapeutics.

Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas

2015 ◽  
Vol 53 (9) ◽  
Author(s):  
Porfyrios Korompelis ◽  
Christina Piperi ◽  
Christos Adamopoulos ◽  
Georgia Dalagiorgou ◽  
Penelope Korkolopoulou ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Uterine Leiomyomas ◽  
Angiogenic Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Protein Levels ◽  
Cellular Hypertrophy ◽  
Tissue Specimens ◽  
And Control

AbstractLeiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas.Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immunohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography.Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p<0.001, p=0.004, p=0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p=0.021) as well as MMP-9 (p=0.001) peripheral levels in the patient’s group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues.This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance.

scholarly journals VASCULAR ENDOTHELIAL GROWTH FACTOR IN CHILDREN WITH THALASSEMIA MAJOR PDF

2013 ◽  
Vol 5 (1) ◽  
pp. e2013044 ◽  
Author(s):  
Sameh Samir Fahmey ◽  
Hassan Naguib ◽  
Sanna Abdelshafy ◽  
Rasha Alashry
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Blood Transfusion ◽  
Elevated Serum ◽  
Thalassemia Major ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Endothelial Growth Factor ◽  
Vegf Level

Background: The β-Thalassemia syndromes are the most common hereditary chronic hemolytic anemia due to impaired globin chain synthesis.  Vascular endothelial growth factor (VEGF) plays several roles in angiogenesis which is a crucial process in the pathogenesis of several inflammatory, autoimmune and malignant diseases .Endothelial damage and inflammation make a significant contribution to the pathophysiology of β-thalassemia. Purpose: The aim of the study was to assess serum VEGF level in children with beta-thalassemia major as a marker of angiogenesis. Methods: Blood samples were collected from 40 patients with thalassemia major and 10 healthy controls and assayed for VEGF by enzyme-linked immunosorbent assay. Results: VEGF level was significantly higher in patients with β-Thalassemia major than healthy controls (p=0.001).In addition, VEGF level was higher in splenectomised thalassemic patients than non splenectomised ones (p=0.001) .However, there were a positive correlation between VEGF and chelation starting age (p=0.008) and a negative correlation between VEGF and frequency of blood transfusion (p=0.002). Conclusion: thalassemia patients, especially splenectomized, have elevated serum levels of VEGF. Early chelation and regular blood transfusion help to decrease serum VEGF and the risk of angiogenesis.  

scholarly journals PEDF expression regulates the proangiogenic and proinflammatory phenotype of the lung endothelium

2014 ◽  
Vol 306 (7) ◽  
pp. L620-L634 ◽  
Author(s):  
Eui Seok Shin ◽  
Christine M. Sorenson ◽  
Nader Sheibani
Keyword(s):  
Pigment Epithelium ◽  
Cell Types ◽  
Vascular Endothelial ◽  
Multifunctional Protein ◽  
Vascular Walls ◽  
Pigment Epithelium Derived Factor ◽  
Lung Endothelium ◽  
Oxide Synthase ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Growth Factor

Pigment epithelium-derived factor (PEDF) is a multifunctional protein with important roles in regulation of inflammation and angiogenesis. It is produced by various cell types, including endothelial cells (EC). However, the cell autonomous impact of PEDF on EC function needs further investigation. Lung EC prepared from PEDF-deficient (PEDF−/−) mice were more migratory and failed to undergo capillary morphogenesis in Matrigel compared with wild type (PEDF+/+) EC. Although no significant differences were observed in the rates of apoptosis in PEDF−/− EC compared with PEDF+/+ cells under basal or stress conditions, PEDF−/− EC proliferated at a slower rate. PEDF−/− EC also expressed increased levels of proinflammatory markers, including vascular endothelial growth factor, inducible nitric oxide synthase, vascular cell adhesion molecule-1, as well as altered cellular junctional organization, and nuclear localization of β-catenin. The PEDF−/− EC were also more adhesive, expressed decreased levels of thrombospondin-2, tenascin-C, and osteopontin, and increased fibronectin. Furthermore, we showed lungs from PEDF−/− mice exhibited increased expression of macrophage marker F4/80, along with increased thickness of the vascular walls, consistent with a proinflammatory phenotype. Together, our data suggest that the PEDF expression makes significant contribution to modulation of the inflammatory and angiogenic phenotype of the lung endothelium.

scholarly journals Viral and cellular cytokines in AIDS-related malignant lymphomatous effusions

Blood ◽  
2000 ◽  
Vol 96 (4) ◽  
pp. 1599-1601 ◽  
Author(s):  
Yoshiyasu Aoki ◽  
Robert Yarchoan ◽  
James Braun ◽  
Aikichi Iwamoto ◽  
Giovanna Tosato
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Human Immunodeficiency Virus ◽  
Potential Role ◽  
Kaposi Sarcoma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Immunodeficiency Virus ◽  
Endothelial Growth Factor ◽  
Primary Effusion Lymphomas

Abstract Kaposi sarcoma-associated herpesvirus encodes viral IL-6 (vIL-6). To investigate the potential role of vIL-6 in the pathogenesis of human immunodeficiency virus (HIV)- related primary effusion lymphomas (PEL), a sensitive enzyme-linked immunosorbent assay was developed for vIL-6 and applied to the study of PEL. Whereas vIL-6 was detectable in 6 of 8 PEL effusions (range, 1390-66 630 pg/mL), it was not detectable in any of the control effusions. As expected, all PEL effusions contained human IL-6 (range, 957-37 494 pg/mL), and 7 of 8 contained detectable human IL-10 (range, 66-2,521,297 pg/mL). Human and vIL-6 have previously been shown to induce vascular endothelial growth factor, which in turn can increase vascular permeability. The results of the current study suggest that these cytokines play a central role in the pathogenesis and manifestations of PEL.

scholarly journals Intervention Effect of Electroacupuncture Combined with EPCs Transplantation on the Mice in Aging Model

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Mei Wen
Keyword(s):  
Liver Tissue ◽  
Vascular Endothelial ◽  
Vascular Aging ◽  
Vascular Endothelial Function ◽  
Vegf Expression ◽  
Intervention Effect ◽  
Protein Levels ◽  
Tissue Fluorescence ◽  
Endothelial Growth Factor

The results of this experiment suggested that electroacupuncture promotes the endothelialization of liver endothelial progenitor cells (EPCs) for mice in D-gal model and improves the repair of vascular endothelial function, as well as increasing the vascular endothelial growth factor (VEGF) expression in liver tissue fluorescence and KL protein levels. Also, it reduces the malondialdehyde (MDA) activity and delays vascular aging and even overall aging. Results showed that the in vivo fluorescence intensity for D-gal EA group was significantly lower than that of D-gal group,P<0.05; VEGF fluorescence expression in liver tissue for D-gal EA group was significantly higher than that for D-gal group,P<0.05; KL protein content in liver tissue for D-gal EA group was significantly higher than that for D-gal group,P<0.05; MDA activity for D-gal EA group was significantly lower than that for D-gal group,P<0.05.

scholarly journals A study of vascular endothelial growth factor in the cord blood of pre-eclamptics and healthy pregnant women

2017 ◽  
Vol 8 (1) ◽  
pp. 21-25
Author(s):  
Anita Rawat ◽  
Anil Kumar Gangwar ◽  
Archana Ghildiyal ◽  
Neena Srivastava ◽  
Sunita Tiwari ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cord Blood ◽  
Pregnant Women ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Vascular Endothelial ◽  
Cord Serum ◽  
Endothelial Growth Factor

Background: Pre-eclampsia(PE) is  the  most  frequently encountered  medical  complication  during  pregnancy. In developing countries PE   is a principal cause of maternal mortality. A disturbance  in  the  angiogenic/antiangiogenic  factors  and  in  the  hypoxia/placental re-oxygenation  process,  seems  to  activate a maternal  endothelial  dysfunction.Aims and Objective: To estimate Vascular Endothelial Growth Factor ( VEGF )  level  in the cord blood of healthy and Preeclamptic ( PEc ) pregnant women and to associate this with Preeclamptic pregnancy.Material and Methods: A case-control study ofUmbilical cord serum VEGF levels from women with uncomplicated pregnancies (control group, n=60) and pregnancies complicated by Pre-eclampsia (n=40). VEGF in the cord serum was estimated by SANDWICH Enzyme Linked Immunosorbent Assay method by using ELISA Kit and then compared between the two groups.Results: The mean VEGF concentrations in the women who had pre-eclampsia  (578.62±468.3)  were lower than in the control group( 625.75±533.1) , but the difference was not statistically significant ( p= 0.8548).  Conclusion VEGF plays a key role in the instability between endothelial dysfunction and angiogenesis that occurs during Preeclampsia.  VEGF levels might be a useful tool for the early diagnosis of Pre-eclampsia.Asian Journal of Medical Sciences Vol.8(1) 2017 21-25

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