VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3829-3837 ◽  
Author(s):  
E. Kukk ◽  
A. Lymboussaki ◽  
S. Taira ◽  
A. Kaipainen ◽  
M. Jeltsch ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lymphatic Vessels ◽  
Mouse Lung ◽  
Vascular Endothelial ◽  
Related Factors ◽  
C Protein ◽  
Lymphatic Vasculature ◽  
Endothelial Growth Factor

The vascular endothelial growth factor family has recently been expanded by the isolation of two new VEGF-related factors, VEGF-B and VEGF-C. The physiological functions of these factors are largely unknown. Here we report the cloning and characterization of mouse VEGF-C, which is produced as a disulfide-linked dimer of 415 amino acid residue polypeptides, sharing an 85% identity with the human VEGF-C amino acid sequence. The recombinant mouse VEGF-C protein was secreted from transfected cells as VEGFR-3 (Flt4) binding polypeptides of 30–32x10(3) Mr and 22–23x10(3) Mr which preferentially stimulated the autophosphorylation of VEGFR-3 in comparison with VEGFR-2 (KDR). In in situ hybridization, mouse VEGF-C mRNA expression was detected in mesenchymal cells of postimplantation mouse embryos, particularly in the regions where the lymphatic vessels undergo sprouting from embryonic veins, such as the perimetanephric, axillary and jugular regions. In addition, the developing mesenterium, which is rich in lymphatic vessels, showed strong VEGF-C expression. VEGF-C was also highly expressed in adult mouse lung, heart and kidney, where VEGFR-3 was also prominent. The pattern of expression of VEGF-C in relation to its major receptor VEGFR-3 during the sprouting of the lymphatic endothelium in embryos suggests a paracrine mode of action and that one of the functions of VEGF-C may be in the regulation of angiogenesis of the lymphatic vasculature.

scholarly journals YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling

Development ◽  
2020 ◽  
Vol 147 (23) ◽  
pp. dev195453
Author(s):  
Boksik Cha ◽  
Yen-Chun Ho ◽  
Xin Geng ◽  
Md. Riaj Mahamud ◽  
Lijuan Chen ◽  
...  
Keyword(s):  
Feedback Loop ◽  
Lymphatic Vessels ◽  
Vascular Endothelial ◽  
Valve Development ◽  
Prox1 Expression ◽  
Homeobox Transcription Factor ◽  
Lymphatic Vasculature ◽  
Factor C ◽  
Endothelial Growth Factor ◽  
First Time

ABSTRACTLymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 is necessary for the development of lymphatic vessels, lymphatic valves (LVs) and lymphovenous valves (LVVs). We and others previously reported a feedback loop between PROX1 and vascular endothelial growth factor-C (VEGF-C) signaling. PROX1 promotes the expression of the VEGF-C receptor VEGFR3 in lymphatic endothelial cells (LECs). In turn, VEGF-C signaling maintains PROX1 expression in LECs. However, the mechanisms of PROX1/VEGF-C feedback loop remain poorly understood. Whether VEGF-C signaling is necessary for LV and LVV development is also unknown. Here, we report for the first time that VEGF-C signaling is necessary for valve morphogenesis. We have also discovered that the transcriptional co-activators YAP and TAZ are required to maintain PROX1 expression in LVs and LVVs in response to VEGF-C signaling. Deletion of Yap and Taz in the lymphatic vasculature of mouse embryos did not affect the formation of LVs or LVVs, but resulted in the degeneration of these structures. Our results have identified VEGF-C, YAP and TAZ as a crucial molecular pathway in valve development.

scholarly journals The Roles of Non-Coding RNAs in Tumor-Associated Lymphangiogenesis

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3290
Author(s):  
Khairunnisa’ Md Yusof ◽  
Rozita Rosli ◽  
Maha Abdullah ◽  
Kelly A. Avery-Kiejda
Keyword(s):  
Growth Factor ◽  
Lymphatic Vessels ◽  
Vascular Endothelial ◽  
Lymphatic Circulation ◽  
Tumor Lymphangiogenesis ◽  
Lymphatic Vasculature ◽  
Lymphatic Development ◽  
Non Coding Rnas ◽  
Endothelial Growth Factor ◽  
Regulation Of Growth

Lymphatic vessels are regarded as the ”forgotten” circulation. Despite this, growing evidence has shown significant roles for the lymphatic circulation in normal and pathological conditions in humans, including cancers. The dissemination of tumor cells to other organs is often mediated by lymphatic vessels that serve as a conduit and is often referred to as tumor-associated lymphangiogenesis. Some of the most well-studied lymphangiogenic factors that govern tumor lymphangiogenesis are the vascular endothelial growth factor (VEGF-C/D and VEGFR-2/3), neuroplilin-2 (NRP2), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF), to name a few. However, recent findings have illustrated that non-coding RNAs are significantly involved in regulating gene expression in most biological processes, including lymphangiogenesis. In this review, we focus on the regulation of growth factors and non-coding RNAs (ncRNAs) in the lymphatic development in normal and cancer physiology. Then, we discuss the lymphangiogenic factors that necessitate tumor-associated lymphangiogenesis, with regards to ncRNAs in various types of cancer. Understanding the different roles of ncRNAs in regulating lymphatic vasculature in normal and cancer conditions may pave the way towards the development of ncRNA-based anti-lymphangiogenic therapy.

Characterization of a drug-targetable allosteric site regulating vascular endothelial growth factor signaling

Angiogenesis ◽  
2018 ◽  
Vol 21 (3) ◽  
pp. 533-543 ◽  
Author(s):  
Katherine M. Thieltges ◽  
Dragana Avramovic ◽  
Chayne L. Piscitelli ◽  
Sandra Markovic-Mueller ◽  
Hans Kaspar Binz ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Growth Factor Signaling ◽  
Vascular Endothelial ◽  
Allosteric Site ◽  
Endothelial Growth Factor

Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues

1993 ◽  
Vol 264 (4) ◽  
pp. C995-C1002 ◽  
Author(s):  
W. T. Monacci ◽  
M. J. Merrill ◽  
E. H. Oldfield
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
In Situ Hybridization ◽  
Rat Tissues ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Organ Specific ◽  
Normal Rat ◽  
Endothelial Growth Factor ◽  
The Brain

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a approximately 43-kDa secreted protein that has been shown in bioassays to induce endothelial proliferation, angiogenesis, and capillary hyperpermeability. VPF has been suggested to play an important role in the physiology of normal vasculature. To further elucidate the natural functions of VPF in vivo, the expression of VPF in normal tissues was examined using Northern blot analysis and in situ hybridization histochemistry. VPF mRNA is expressed in the brain, kidney, liver, lung, and spleen of the healthy adult rat. On Northern blots, the relative abundance of VPF mRNA observed in these tissues was highest in the lung and lowest in the spleen. As determined by in situ hybridization, the patterns of VPF expression are organ specific. Hybridization of an antisense VPF probe was concentrated in the cerebellar granule cell layer of the brain and in the glomeruli and tubules of the kidney. In the liver and lung, intense hybridization was observed homogeneously throughout both tissues, demonstrating that VPF mRNA is present in virtually every hepatocyte and pulmonary alveolar cell. Hybridization to the spleen was weaker and more diffuse. The widespread expression and organ-specific distribution of VPF mRNA in normal rat tissues supports the suggestion of an extensive role for this factor in the physiology of normal vasculature.

scholarly journals Effect of Serum Copper on Circulating Angiogenesis-Related Factors in Women with Preeclampsia

2019 ◽  
Author(s):  
Khalid Najm Nadheer ◽  
Zohreh Zahraei ◽  
Hussein Al-Hakeim
Keyword(s):  
Pregnant Women ◽  
Serum Copper ◽  
Control Group ◽  
Vascular Endothelial ◽  
Related Factors ◽  
Soluble Endoglin ◽  
Iraqi Women ◽  
Endothelial Integrity ◽  
And Control ◽  
Endothelial Growth Factor

Preeclampsia (PE) is characterized by a series of clinical features such as hypertension and proteinuria associated with endothelial dysfunction and the impairment of placenta vascular endothelial integrity. This study aimed to investigate the effect of serum copper (Cu) level on some angiogenesis-related factors including vascular endothelial growth factor-A (VEGF-A), soluble Fms-like tyrosine kinase-1 (sVEGF-R1), soluble endoglin (sEng) and cerruloplasmin (Cp) in Iraqi women with preeclampsia (PE) and control pregnant women. Therefore, 60 women with PE in addition to 30 healthy pregnant women were enrolled in the study. Serum concentration of sEng, VEGF-A, sVEGF-R1, and Cu in PE group significantly increased (p<0.05) in the PE group compared with that in the control group. Increased production of antiangiogenic factors, soluble VEGF-A and sEng contribute to the pathophysiology of PE, indicating the involvement of these parameters in the angiogenic balance in patients with PE. Tests for between-subject effects showed that the circulating angiogenesis factors and Cu were significantly associated with the presence of PE. Serum Cu level was significantly correlated with VEGF- A and VEGF-R1 levels but not with sEng. Multiple regression analysis revealed that only Cp and BP can significantly predict the complications in women with PE. In conclusion, serum Cu has a role in the angiogenesis in women with PE and may be a new drug target in the prevention or treatment of PE.

scholarly journals Uremic Toxin Lanthionine Interferes with the Transsulfuration Pathway, Angiogenetic Signaling and Increases Intracellular Calcium

2019 ◽  
Vol 20 (9) ◽  
pp. 2269 ◽  
Author(s):  
Carmela Vigorito ◽  
Evgeniya Anishchenko ◽  
Luigi Mele ◽  
Giovanna Capolongo ◽  
Francesco Trepiccione ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Content ◽  
Cell Cultures ◽  
Uremic Toxin ◽  
Vascular Endothelial ◽  
Beneficial Effects ◽  
Transsulfuration Pathway ◽  
Strip Test ◽  
Endothelial Growth Factor

(1) The beneficial effects of hydrogen sulfide (H2S) on the cardiovascular and nervous system have recently been re-evaluated. It has been shown that lanthionine, a side product of H2S biosynthesis, previously used as a marker for H2S production, is dramatically increased in circulation in uremia, while H2S release is impaired. Thus, lanthionine could be classified as a novel uremic toxin. Our research was aimed at defining the mechanism(s) for lanthionine toxicity. (2) The effect of lanthionine on H2S release was tested by a novel lead acetate strip test (LAST) in EA.hy926 cell cultures. Effects of glutathione, as a redox agent, were assayed. Levels of sulfane sulfur were evaluated using the SSP4 probe and flow cytometry. Protein content and glutathionylation were analyzed by Western Blotting and immunoprecipitation, respectively. Gene expression and miRNA levels were assessed by qPCR. (3) We demonstrated that, in endothelial cells, lanthionine hampers H2S release; reduces protein content and glutathionylation of transsulfuration enzyme cystathionine-β-synthase; modifies the expression of miR-200c and miR-423; lowers expression of vascular endothelial growth factor VEGF; increases Ca2+ levels. (4) Lanthionine-induced alterations in cell cultures, which involve both sulfur amino acid metabolism and calcium homeostasis, are consistent with uremic dysfunctional characteristics and further support the uremic toxin role of this amino acid.

scholarly journals Modular protein-oligonucleotide signal exchange

2020 ◽  
Vol 48 (12) ◽  
pp. 6431-6444
Author(s):  
Deepak K Agrawal ◽  
Rebecca Schulman
Keyword(s):  
Specific Protein ◽  
Vascular Endothelial ◽  
Complementary Dna ◽  
Exchange Processes ◽  
Dna Strand Displacement ◽  
Specific Proteins ◽  
Dna Strand ◽  
Endothelial Growth Factor ◽  
Signal Exchange

Abstract While many methods are available to measure the concentrations of proteins in solution, the development of a method to quantitatively report both increases and decreases in different protein concentrations in real-time using changes in the concentrations of other molecules, such as DNA outputs, has remained a challenge. Here, we present a biomolecular reaction process that reports the concentration of an input protein in situ as the concentration of an output DNA oligonucleotide strand. This method uses DNA oligonucleotide aptamers that bind either to a specific protein selectively or to a complementary DNA oligonucleotide reversibly using toehold-mediated DNA strand-displacement. It is possible to choose the sequence of output strand almost independent of the sensing protein. Using this strategy, we implemented four different exchange processes to report the concentrations of clinically relevant human α-thrombin and vascular endothelial growth factor using changes in concentrations of DNA oligonucleotide outputs. These exchange processes can operate in tandem such that the same or different output signals can indicate changes in concentration of distinct or identical input proteins. The simplicity of our approach suggests a pathway to build devices that can direct diverse output responses in response to changes in concentrations of specific proteins.

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