scholarly journals Possible co-option of a VEGF-driven tubulogenesis program for biomineralization in echinoderms

2019 ◽  
Author(s):  
Miri Morgulis ◽  
Tsvia Gildor ◽  
Modi Roopin ◽  
Noa Sher ◽  
Assaf Malik ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Sea Urchin ◽  
Regulatory Networks ◽  
Critical Role ◽  
Vascular Endothelial ◽  
Upstream Gene ◽  
Vegf Signaling ◽  
Vegf Pathway ◽  
Endothelial Growth Factor

AbstractBiomineralization is the process in which living organisms use minerals to form hard structures that protect and support them. Biomineralization is believed to have evolved rapidly and independently in different phyla utilizing existing components used for other purposes. The mechanistic understanding of the regulatory networks that drive biomineralization and their evolution is far from clear. The sea urchin skeletogenesis is an excellent model system for studying both gene regulation and mineral uptake and deposition. The sea urchin calcite spicules are formed within a tubular cavity generated by the skeletogenic cells under the control the vascular endothelial growth factor (VEGF) signaling. The VEGF pathway controls tubulogenesis and vascularization across metazoans while its regulation of biomineralization was only observed in echinoderms. Despite the critical role of VEGF signaling in sea urchin spiculogenesis, the downstream program it activates was largely unknown. Here we study the cellular and molecular machinery activated by the VEGF pathway during sea urchin spiculogenesis and reveal multiple parallels to the regulation of tubulogenesis during vertebrate vascularization. Human VEGF rescues sea urchin VEGF knock-down; VEGF-dependent vesicle deposition plays a significant role in both systems and sea urchin VEGF signaling activates hundreds of genes including biomineralization and vascularization genes. Five upstream transcription factors and three signaling genes active in spiculogenesis are homologous to vertebrate factors that regulate vascularization. Overall, our findings suggest that sea urchin spiculogenesis and vertebrate vascularization diverged from a common ancestral tubulogenesis program, broadly adapted for vascularization and specifically co-opted for biomineralization in the echinoderm phylum.Significance statementThe sea urchin calcite spicules and vertebrate blood vessels are quite distinct in their function, yet both have a tubular structure and are controlled by the vascular endothelial growth factor (VEGF) pathway. Here we study the downstream program by which VEGF pathway drives sea urchin spiculogenesis and find remarkable similarities to the control of vertebrate vascularization. The similarities are observed both in the upstream gene regulatory network, in the downstream effector genes and the cellular processes that VEGF signaling controls at the site of the calcite spicule formation. We speculate that sea urchin spiculogenesis and vertebrate vascularization diverged from a common ancestral tubulogenesis program that was co-opted for biomineralization in the echinoderm phylum.

scholarly journals Expression of Tumor-Derived Vascular Endothelial Growth Factor and Its Receptors Is Associated With Outcome in Early Squamous Cell Carcinoma of the Lung

2012 ◽  
Vol 30 (10) ◽  
pp. 1129-1136 ◽  
Author(s):  
María J. Pajares ◽  
Jackeline Agorreta ◽  
Marta Larrayoz ◽  
Aurélien Vesin ◽  
Teresa Ezponda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Squamous Cell Carcinoma ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Vegf Pathway ◽  
Cell Expression ◽  
Endothelial Growth Factor ◽  
Histologic Subtypes

PurposeAntiangiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have yielded more modest clinical benefit to patients with non–small-cell lung cancer (NSCLC) than initially expected. Clinical data suggest a distinct biologic role of the VEGF pathway in the different histologic subtypes of lung cancer. To clarify the influence of histologic differentiation in the prognostic relevance of VEGF-mediated signaling in NSCLC, we performed a concomitant analysis of the expression of three key elements of the VEGF pathway in the earliest stages of the following two principal histologic subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC).Patients and MethodsWe evaluated tumor cell expression of VEGF, VEGF receptor (VEGFR) 1, and VEGFR2 using automatic immunostaining in a series of 298 patients with early-stage NSCLC recruited as part of the multicenter European Early Lung Cancer Detection Group project. A score measuring the VEGF signaling pathway was calculated by adding the tumor cell expression value of VEGF and its two receptors. The results were validated in two additional independent cohorts of patients with NSCLC.ResultsThe combination of high VEGF, VEGFR1, and VEGFR2 protein expression was associated with lower risk of disease progression in early SCC (univariate analysis, P = .008; multivariate analysis, hazard ratio, 0.62; 95% CI, 0.42 to 0.92; P = .02). The results were validated in two independent patient cohorts, confirming the favorable prognostic value of high VEGF signaling score in early lung SCC.ConclusionOur results clearly indicate that the combination of high expression of the three key elements in the VEGF pathway is associated with a good prognosis in patients with early SCC but not in patients with ADC.

scholarly journals Vascular Endothelial Growth Factor as an Immediate-Early Activator of UV-induced Skin Injury

2020 ◽  
Author(s):  
Stella P. Hartono ◽  
Victoria M. Bedell ◽  
Sk. Kayum Alam ◽  
Madelyn O’Gorman ◽  
MaKayla Serres ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
The United States ◽  
Uv Exposure ◽  
Therapeutic Window ◽  
Vascular Endothelial ◽  
Acute Effects ◽  
Vegf Signaling ◽  
Vegf Pathway ◽  
Endothelial Growth Factor

ABSTRACTThe negative health consequences of acute ultraviolet (UV) exposure are evident, with reports of 30,000 emergency room visits annually to treat the effects of sunburn in the United States alone. Acute effects of sunburn include erythema, edema, and severe pain, and chronic overexposure to UV radiation can lead to skin cancer. While the pain associated with the acute effects of sunburn may be relieved by current interventions, existing post-sunburn treatments are not capable of reversing the cumulative and long-term pathological effects of UV exposure, an unmet clinical need. Here we show that activation of the vascular endothelial growth factor (VEGF) pathway is a direct and immediate consequence of acute UV exposure, and activation of VEGF signaling is necessary for the initiating the acute pathological effects of sunburn. In UV-exposed human subjects, VEGF signaling is activated within hours. Topical delivery of VEGF pathway inhibitors, targeted against the ligand VEGF-A (gold nanoparticles conjugated with anti-VEGF antibodies) and small molecule antagonists of VEGF receptor signaling, prevent the development of erythema and edema in UV-exposed mice. Collectively, these findings suggest targeting VEGF signaling may reduce the subsequent inflammation and pathology associated with UV-induced skin damage, which reveals a new post-exposure therapeutic window to potentially inhibit the known detrimental effects of UV on human skin.

scholarly journals Possible cooption of a VEGF-driven tubulogenesis program for biomineralization in echinoderms

2019 ◽  
Vol 116 (25) ◽  
pp. 12353-12362 ◽  
Author(s):  
Miri Morgulis ◽  
Tsvia Gildor ◽  
Modi Roopin ◽  
Noa Sher ◽  
Assaf Malik ◽  
...  
Keyword(s):  
Sea Urchin ◽  
Regulatory Networks ◽  
Critical Role ◽  
Internal Cavity ◽  
Vegf Signaling ◽  
Molecular Machinery ◽  
Vegf Pathway ◽  
Living Organisms ◽  
Hard Structures ◽  
Endothelial Growth Factor

Biomineralization is the process by which living organisms use minerals to form hard structures that protect and support them. Biomineralization is believed to have evolved rapidly and independently in different phyla utilizing preexisting components. The mechanistic understanding of the regulatory networks that drive biomineralization and their evolution is far from clear. Sea urchin skeletogenesis is an excellent model system for studying both gene regulation and mineral uptake and deposition. The sea urchin calcite spicules are formed within a tubular cavity generated by the skeletogenic cells controlled by vascular endothelial growth factor (VEGF) signaling. The VEGF pathway is essential for biomineralization in echinoderms, while in many other phyla, across metazoans, it controls tubulogenesis and vascularization. Despite the critical role of VEGF signaling in sea urchin spiculogenesis, the downstream program it activates was largely unknown. Here we study the cellular and molecular machinery activated by the VEGF pathway during sea urchin spiculogenesis and reveal multiple parallels to the regulation of vertebrate vascularization. Human VEGF rescues sea urchin VEGF knockdown, vesicle deposition into an internal cavity plays a significant role in both systems, and sea urchin VEGF signaling activates hundreds of genes, including biomineralization and interestingly, vascularization genes. Moreover, five upstream transcription factors and three signaling genes that drive spiculogenesis are homologous to vertebrate factors that control vascularization. Overall, our findings suggest that sea urchin spiculogenesis and vertebrate vascularization diverged from a common ancestral tubulogenesis program, broadly adapted for vascularization and specifically coopted for biomineralization in the echinoderm phylum.

scholarly journals Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Xi Guo ◽  
Hong Yi ◽  
Tin Chiu Li ◽  
Yu Wang ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Critical Role ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Underlying Mechanisms ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.

Expression pattern of vascular endothelial growth factor 2 during sea urchin development

2013 ◽  
Vol 13 (8) ◽  
pp. 402-406 ◽  
Author(s):  
Yulia O. Kipryushina ◽  
Konstantin V. Yakovlev ◽  
Milana A. Kulakova ◽  
Nelly A. Odintsova
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Expression Pattern ◽  
Sea Urchin ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Characterization of the vasculogenic block in the absence of vascular endothelial growth factor-A

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 1979-1987 ◽  
Author(s):  
Victoria L. Bautch ◽  
Sambra D. Redick ◽  
Aaron Scalia ◽  
Marco Harmaty ◽  
Peter Carmeliet ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Embryonic Stem ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Homozygous Mutant ◽  
Endothelial Growth Factor ◽  
Rna Levels

Abstract Vascular endothelial growth factor (VEGF) signaling is required for both differentiation and proliferation of vascular endothelium. Analysis of differentiated embryonic stem cells with one or both VEGF-A alleles deleted showed that both the differentiation and the expansion of endothelial cells are blocked during vasculogenesis. Blood island formation was reduced by half in hemizygous mutant VEGF cultures and by 10-fold in homozygous mutant VEGF cultures. Homozygous mutant cultures could be partially rescued by the addition of exogenous VEGF. RNA levels for the endothelial adhesion receptors ICAM-2 and PECAM were reduced in homozygous mutant cultures, but ICAM-2 RNA levels decreased substantially, whereas PECAM RNA levels remained at hemizygous levels. The quantitative data correlated with the antibody staining patterns because cells that were not organized into vessels expressed PECAM but not ICAM-2. These PECAM+ cell clumps accumulated in mutant cultures as vessel density decreased, suggesting that they were endothelial cell precursors blocked from maturation. A subset of PECAM+ cells in clumps expressed stage-specific embryonic antigen-1 (SSEA-1), and all were ICAM-2(−) and CD34(−), whereas vascular endothelial cells incorporated into vessels were PECAM(+), ICAM-2(+), CD34(+), and SSEA-1(−). Analysis of flk-1 expression indicated that a subset of vascular precursor cells coexpressed PECAM and flk-1. These data suggest that VEGF signaling acts in a dose-dependent manner to affect both a specific differentiation step and the subsequent expansion of endothelial cells.

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