scholarly journals Blockade of in vivo VEGF-mediated angiogenesis by antisense gene therapy: role of Flk-1 and Flt-1 receptors

2002 ◽  
Vol 282 (1) ◽  
pp. H194-H204 ◽  
Author(s):  
Geneviève S. Marchand ◽  
Nicolas Noiseux ◽  
Jean-François Tanguay ◽  
Martin G. Sirois
Keyword(s):  
Blood Vessels ◽  
Fetal Liver ◽  
Capillary Blood ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Antisense Gene ◽  
Endothelial Growth Factor ◽  
Phosphate Buffered Saline

Angiogenesis, the formation of new blood vessels from preexisting ones, is a critical component of various pathologies such as tumor progression, rheumatoid arthritis, and retinopathies. Vascular endothelial growth factor (VEGF) is a mitogenic and chimiotactic factor capable of inducing angiogenesis through the activation of its receptors, fetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-1 (Flt-1), expressed on endothelial cells. The purpose of the present study was to assess if a treatment with antisense (AS) oligonucleotides directed against VEGF receptors Flk-1 or Flt-1 mRNA could prevent VEGF-mediated angiogenesis. With the use of miniosmotic pumps, phosphate-buffered saline, VEGF, or VEGF combined with AS-Flk-1, AS-Flt-1, or AS-scrambled oligonucleotides were released in mouse testis for 14 days. VEGF (1, 2.5, and 5 μg) increased the formation of new capillary blood vessels by 236, 246, and 287%, respectively. The combination of AS-Flk-1 or AS-Flt-1 (200 μg) to VEGF (2.5 μg) reduced by 87 and 85% the formation of new blood vessels, respectively, and the expression of their corresponding proteins. These data demonstrate the therapeutical potential of AS-Flk-1 or AS-Flt-1 to prevent VEGF-mediated angiogenesis in vivo.

scholarly journals Role of vascular endothelial growth factor in inducing production of angiopoetin-1 – in vivo study in Fisher rats

2017 ◽  
Vol 68 (4) ◽  
pp. 326-329
Author(s):  
Piotr Barć ◽  
Tomasz Płonek ◽  
Dagmara Baczyńska ◽  
Artur Pupka ◽  
Wojciech Witkiewicz ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
In Vivo Study ◽  
Vascular Endothelial ◽  
Angiopoetin 1 ◽  
Endothelial Growth Factor

Stathmin 1 plays a role in endometrial decidualisation by regulating hypoxia inducible factor-1α and vascular endothelial growth factor during embryo implantation

2017 ◽  
Vol 29 (8) ◽  
pp. 1530 ◽  
Author(s):  
Jinhai Gou ◽  
Jia Jia ◽  
Juntao Feng ◽  
Xia Zhao ◽  
Tao Yi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Embryo Implantation ◽  
Hypoxia Inducible Factor ◽  
Implantation Site ◽  
Vascular Endothelial ◽  
Stathmin 1 ◽  
Endothelial Growth Factor

The aim of the present study was to explore the potential mechanism underlying stathmin 1 (Stmn1) regulation of embryo implantation, as a continuation of previous proteomic research. Adult healthy female mice were mated naturally with fertile males. Murine uterine tissue was collected during the peri-implantation period. Local expression of Stmn1 during embryo implantation was detected by immunohistochemistry (IHC), which showed that Stmn1 was extensively expressed in endometrial glandular epithelium, vascular endothelium, luminal epithelium and the underlying stromal cells at the implantation site on Day 5. The role of Stmn1 during embryo implantation was evaluated by transient knockdown of Stmn1 in vivo using short interference (si) RNA, and some associated factors including Akt, phosphorylated (p-) Akt, hypoxia-inducible factor (HIF)-1α, prolactin (PRL), insulin-like growth factor binding protein (IGFBP) 1 and vascular endothelial growth factor (VEGF) were examined by western blotting analysis and ELISA. The number of embryos implanted after Stmn1-siRNA infusion into the lumen of one uterine horn was lower than that with normal pregnancies (2.2 ± 1.5 vs 8.6 ± 0.5 respectively; P < 0.05). The expression of VEGF, HIF-1α, p-Akt and the decidualisation biomarkers PRL and IGFBP 1 was upregulated at the implantation site on Day 5, but downregulated after Stmn1-siRNA infusion. These findings suggest that during embryo implantation, knockdown of Stmn1 suppresses decidualisation by inhibiting the expression of p-Akt, HIF-1α and VEGF, thus leading to impaired embryo implantation. These findings provide clues for understanding the complicated process of embryo implantation and the potential role of Stmn1 during embryo implantation.

scholarly journals Thrombospondin-1 Is Downregulated by Anoxia and Suppresses Tumorigenicity of Human Glioblastoma Cells

2000 ◽  
Vol 191 (10) ◽  
pp. 1789-1798 ◽  
Author(s):  
Mirna Tenan ◽  
Giulia Fulci ◽  
Michele Albertoni ◽  
Annie-Claire Diserens ◽  
Marie-France Hamou ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Blood Vessels ◽  
Vascular Endothelial ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Thrombospondin 1 ◽  
Natural Inhibitor ◽  
Endothelial Growth Factor

Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results from a disruption of the balance between stimulatory and inhibitory factors. Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo.

scholarly journals Interleukin-37b inhibits the growth of murine endometriosis-like lesions by regulating proliferation, invasion, angiogenesis and inflammation

2020 ◽  
Vol 26 (4) ◽  
pp. 240-255
Author(s):  
Yongpei He ◽  
Ting Xiong ◽  
Fang Guo ◽  
Zhenzhen Du ◽  
Yixian Fan ◽  
...  
Keyword(s):  
Early Stage ◽  
Inflammatory Factors ◽  
Epithelial Cell Line ◽  
Vascular Endothelial ◽  
Gynecological Disease ◽  
Endothelial Growth Factor ◽  
In Vitro Treatment

Abstract Endometriosis is a gynecological disease with abnormal expression of interleukin (IL)-37 which can suppress inflammation and the immune system. Here we investigated the role of the IL-37b splice variant in endometriosis in vivo and in vitro. In a murine model of endometriosis, in vivo administration of IL-37b significantly inhibited the development of lesions judged by the number (P = 0.0213), size (P = 0.0130) and weight (P = 0.0152) of lesions. IL-37b had no effect on the early stage of lesion formation, however administration in the growth stage of lesions decreased the number (P = 0.0158), size (P = 0.0158) and weight (P = 0.0258) of lesions compared with PBS control, an effect that was not reversed by macrophage depletion. Expressions of inflammatory factors, matrix metalloproteinases and vascular endothelial growth factor-A mRNA/protein were significantly inhibited in ectopic lesions following IL-37b administration, and in uterine segments treated in vitro. In vitro treatment of uterine segments with IL-37b inhibited phosphorylation of Akt and Erk1/2 in uterine segments. Isolated mouse endometrial stromal treated with IL-37b and transfected with pIL-37b plasmid got suppressed cell proliferation, invasion, angiogenesis and the expression of inflammatory factors. In addition, transfection with pIL-37b significantly decreased the phosphorylation of Akt and Erk1/2. IL-37b also inhibited proliferation and the expression of inflammatory and angiogenesis factors in epithelial cell line RL95–2. These findings suggest that IL-37b may inhibit the growth of lesions by regulating proliferation, invasion, angiogenesis and inflammation through Akt and Erk1/2 signaling pathway.

VEGF promotes vascular sympathetic innervation

2008 ◽  
Vol 294 (6) ◽  
pp. H2646-H2652 ◽  
Author(s):  
Stephen B. Marko ◽  
Deborah H. Damon
Keyword(s):  
Blood Vessels ◽  
Sympathetic Innervation ◽  
Nerve Fibers ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Sympathetic Nerve Fibers ◽  
Endothelial Growth Factor ◽  
Immunohistochemical Analyses

The sympathetic nervous system, via postganglionic innervation of blood vessels and the heart, is an important determinant of cardiovascular function. The mechanisms underlying sympathetic innervation of targets are not fully understood. This study tests the hypothesis that target-derived vascular endothelial growth factor (VEGF) promotes sympathetic innervation of blood vessels. Western blot and immunohistochemical analyses indicate that VEGF is produced by vascular cells in arteries and that VEGF receptors are expressed on sympathetic nerve fibers innervating arteries. In vitro, exogenously added VEGF and VEGF produced by vascular smooth muscle cells (VSMCs) in sympathetic neurovascular cocultures inhibited semaphorin 3A (Sema3A)-induced collapse of sympathetic growth cones. In the absence of Sema3A, VEGF and VSMCs also increased growth cone area. These effects were mediated via VEGF receptor 1. In vivo, the neutralization of VEGF inhibited the reinnervation of denervated femoral arteries. These data demonstrate that target-derived VEGF plays a previously unrecognized role in promoting the growth of sympathetic axons.

The Role of Vascular Endothelial Growth Factor in the Tissue Specific in Vivo Growth of Prostate Cancer Cells

2001 ◽  
Vol 18 (4) ◽  
pp. 287-302 ◽  
Author(s):  
Tracey Krupski ◽  
Michael A. Harding ◽  
Michael E. Herce ◽  
Kay M. Gulding ◽  
Mark H. Stoler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Vascular Endothelial ◽  
Prostate Cancer Cells ◽  
In Vivo Growth ◽  
Endothelial Growth Factor

Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells

2000 ◽  
Vol 278 (6) ◽  
pp. F905-F915 ◽  
Author(s):  
John Kanellis ◽  
Scott Fraser ◽  
Marina Katerelos ◽  
David A. Power
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Vascular Endothelial ◽  
Vegf Receptors ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Survival Factor ◽  
Renal Tubular ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) acts primarily as an endothelial cell mitogen via the “endothelial cell-specific” receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR). Only a few nonendothelial cells have been shown to possess functional VEGF receptors. We therefore examined the rat renal tubular epithelial cell line NRK52-E. NRK52-E expressed VEGFR-1 and VEGFR-2 mRNA and protein by RT-PCR, Northern blotting, Western blotting, immunofluorescence, and ligand binding. Serum-starved NRK52-E incubated with VEGF showed a significant increase in [3H]thymidine incorporation compared with control (2.3-fold at 1–10 ng/ml, P < 0.05; 3.3-fold at 50–100 ng/ml, P < 0.01). VEGF also protected NRK52-E from hydrogen peroxide-induced apoptosis and necrosis compared with control (annexin-V-FITC-positive cells, 39 vs. 54%; viable cells, 50.5 vs. 39.7%). Immunohistochemical staining using a variety of antibodies showed expression of both VEGF receptors in normal rat renal tubules in vivo. Because VEGF induced a proliferative and an antiapoptotic response in renal tubular epithelial cells, these data suggest that VEGF may act as a survival factor for renal tubular epithelium in vivo.

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