scholarly journals MicroRNAs in Vascular Eye Diseases

2020 ◽  
Vol 21 (2) ◽  
pp. 649 ◽  
Author(s):  
Chi-Hsiu Liu ◽  
Shuo Huang ◽  
William R. Britton ◽  
Jing Chen
Keyword(s):  
Normal Development ◽  
Molecular Targets ◽  
Eye Diseases ◽  
Vascular Endothelial ◽  
Ocular Neovascularization ◽  
Research Fields ◽  
Novel Targets ◽  
New Treatments ◽  
Endothelial Growth Factor ◽  
Potential Therapeutics

Since the discovery of the first microRNA (miRNA) decades ago, studies of miRNA biology have expanded in many biomedical research fields, including eye research. The critical roles of miRNAs in normal development and diseases have made miRNAs useful biomarkers or molecular targets for potential therapeutics. In the eye, ocular neovascularization (NV) is a leading cause of blindness in multiple vascular eye diseases. Current anti-angiogenic therapies, such as anti-vascular endothelial growth factor (VEGF) treatment, have their limitations, indicating the need for investigating new targets. Recent studies established the roles of various miRNAs in the regulation of pathological ocular NV, suggesting miRNAs as both biomarkers and therapeutic targets in vascular eye diseases. This review summarizes the biogenesis of miRNAs, and their functions in the normal development and diseases of the eye, with a focus on clinical and experimental retinopathies in both human and animal models. Discovery of novel targets involving miRNAs in vascular eye diseases will provide insights for developing new treatments to counter ocular NV.

scholarly journals microRNA-214 Prevents Traits of Cutaneous Squamous Cell Carcinoma via VEGFA and Bcl-2

2020 ◽  
Vol 19 ◽  
pp. 153303382098009
Author(s):  
Xianpeng Ma ◽  
Di Wu ◽  
Xiaodong Zhang ◽  
Xiao Shao ◽  
Guangyao Hu
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cellular Level ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Vascular Endothelial ◽  
Specific Mechanism ◽  
Novel Targets ◽  
Endothelial Growth Factor

Background: Dysregulation of microRNA-214 (miR-214) has been indicated in different tumors. The function of miR-214 in cutaneous squamous cell carcinoma (CSCC) is yet to be deciphered. The current study aimed to investigate the specific mechanism underpinning CSCC development with the involvement of miR-214 and its putative targets. Methods: Microarray analysis of CSCC and adjacent tissues was carried out to filter the most significant downregulated miRNA. Survival analysis of patients was subsequently implemented, followed by miRNA expression determination in CSCC cells. Gain-of-function assays were performed to evaluate its function on cellular level. The targets of the determined miRNA were predicted and their expression in CSCC and adjacent tissues was evaluated. The targeting relationship was analyzed by dual-luciferase assays. Finally, rescue experiments were conducted. Results: miR-214 was reduced in CSCC tissues and cells, and the survival of patients harboring overexpression of miR-214 was higher. miR-214 restoration increased CSCC cell apoptosis, while decreased proliferative, invasive and migratory activities. miR-214 interacted with vascular endothelial growth factor A (VEGFA) and B-cell CLL/lymphoma 2 (Bcl-2). VEGFA and Bcl-2, overexpressed in CSCC tissues and cells, were negatively correlated with miR-214. Moreover, VEGFA and Bcl-2 overexpression reversed the anti-tumor phenotypes of miR-214 on CSCC cells. miR-214 disrupted the Wnt/β-catenin pathway through VEGFA and Bcl-2 in the CSCC cells. Conclusion: Our data demonstrates that miR-214 exerts a suppressing role in CSCC. The discovery of novel targets such as miR-214 and VEGFA/Bcl-2 may facilitate the development of therapeutic options.

scholarly journals Distinct Requirements for Zebrafish Angiogenesis Revealed by aVEGF-AMorphant

Yeast ◽  
2000 ◽  
Vol 1 (4) ◽  
pp. 294-301 ◽  
Author(s):  
Aidas Nasevicius ◽  
Jon Larson ◽  
Stephen C. Ekker
Keyword(s):  
Normal Development ◽  
Developmental Process ◽  
Vascular Endothelial ◽  
Vascular Structure ◽  
Loss Of Function ◽  
Quality Model ◽  
Tissue Remodelling ◽  
Structure Specification ◽  
Endothelial Growth Factor

Angiogenesis is a fundamental vertebrate developmental process that requires signalling by the secreted protein vascular endothelial growth factor-A (VEGF-A).VEGF-Afunctions in the development of embryonic structures, during tissue remodelling and for the growth of tumour-induced vasculature. The study of the role ofVEGF-Aduring normal development has been significantly complicated by the dominant, haplo-insufficient nature ofVEGF-A-targeted mutations in mice. We have used morpholino-based targeted gene knock-down technology to generate a zebrafishVEGF-Amorphant loss of function model. ZebrafishVEGF-Amorphant embryos develop with an enlarged pericardium and with major blood vessel deficiencies. Morphological assessment at 2 days of development indicates a nearly complete absence of both axial and intersegmental vasculature, with no or reduced numbers of circulating red blood cells. Molecular analysis using the endothelial markersfli-1andflk-1at 1 day of development demonstrates a fundamental distinction betweenVEGF-Arequirements for axial and intersegmental vascular structure specification.VEGF-Ais not required for the initial establishment of axial vasculature patterning, whereas all development of intersegmental vasculature is dependent onVEGF-Asignalling. The zebrafish thus serves as a quality model for the study of conserved vertebrate angiogenesis processes during embryonic development.

scholarly journals Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ross O Smith ◽  
Takeshi Ninchoji ◽  
Emma Gordon ◽  
Helder André ◽  
Elisabetta Dejana ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Vascular Permeability ◽  
Geographic Atrophy ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Oxygen Induced Retinopathy ◽  
Age Related ◽  
Endothelial Growth Factor

Edema stemming from leaky blood vessels is common in eye diseases such as age-related macular degeneration and diabetic retinopathy. Whereas therapies targeting vascular endothelial growth factor A (VEGFA) can suppress leakage, side-effects include vascular rarefaction and geographic atrophy. By challenging mouse models representing different steps in VEGFA/VEGF receptor 2 (VEGFR2)-induced vascular permeability, we show that targeting signaling downstream of VEGFR2 pY949 limits vascular permeability in retinopathy induced by high oxygen or by laser-wounding. Although suppressed permeability is accompanied by reduced pathological neoangiogenesis in oxygen-induced retinopathy, similarly sized lesions leak less in mutant mice, separating regulation of permeability from angiogenesis. Strikingly, vascular endothelial (VE)-cadherin phosphorylation at the Y685, but not Y658, residue is reduced when VEGFR2 pY949 signaling is impaired. These findings support a mechanism whereby VE-cadherin Y685 phosphorylation is selectively associated with excessive vascular leakage. Therapeutically, targeting VEGFR2-regulated VE-cadherin phosphorylation could suppress edema while leaving other VEGFR2-dependent functions intact.

scholarly journals Distinct Requirements for Zebrafish Angiogenesis Revealed by a VEGF-A Morphant

Yeast ◽  
2000 ◽  
Vol 1 (4) ◽  
pp. 294-301
Author(s):  
Aidas Nasevicius ◽  
Jon Larson ◽  
Stephen C. Ekker
Keyword(s):  
Normal Development ◽  
Developmental Process ◽  
Vascular Endothelial ◽  
Vascular Structure ◽  
Loss Of Function ◽  
Quality Model ◽  
Tissue Remodelling ◽  
Structure Specification ◽  
Endothelial Growth Factor

Angiogenesis is a fundamental vertebrate developmental process that requires signalling by the secreted protein vascular endothelial growth factor-A (VEGF-A). VEGF-A functions in the development of embryonic structures, during tissue remodelling and for the growth of tumour-induced vasculature. The study of the role of VEGF-A during normal development has been significantly complicated by the dominant, haplo-insufficient nature of VEGF-A-targeted mutations in mice. We have used morpholino-based targeted gene knock-down technology to generate a zebrafish VEGF-A morphant loss of function model. Zebrafish VEGF-A morphant embryos develop with an enlarged pericardium and with major blood vessel deficiencies. Morphological assessment at 2 days of development indicates a nearly complete absence of both axial and intersegmental vasculature, with no or reduced numbers of circulating red blood cells. Molecular analysis using the endothelial markers fli-1 and flk-1 at 1 day of development demonstrates a fundamental distinction between VEGF-A requirements for axial and intersegmental vascular structure specification. VEGF-A is not required for the initial establishment of axial vasculature patterning, whereas all development of intersegmental vasculature is dependent on VEGF-A signalling. The zebrafish thus serves as a quality model for the study of conserved vertebrate angiogenesis processes during embryonic development.

scholarly journals microRNA-214 prevents traits of cutaneous squamous cell carcinoma via VEGFA and Bcl-2

2020 ◽  
Author(s):  
Xianpeng Ma ◽  
Di Wu ◽  
Xiaodong Zhang ◽  
Xiao Shao ◽  
Guangyao Hu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cellular Level ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Vascular Endothelial ◽  
Specific Mechanism ◽  
Tumor Phenotype ◽  
Novel Targets ◽  
Endothelial Growth Factor

Abstract Background Dysregulation of microRNA-214 (miR-214) has been indicated in different tumors. The function of miR-214 in cutaneous squamous cell carcinoma (CSCC) is yet to be deciphered. The current study aimed to investigate the specific mechanism underpinning CSCC development with the involvement of miR-214 and its putative targets. Methods Microarray analysis of CSCC and adjacent tissues was carried out to filter the most significant downregulated miRNA. Survival analysis of patients was subsequently implemented, followed by miRNA expression determination in CSCC cells. Gain-of-function assays were performed to evaluate its function on cellular level. The targets of the determined miRNA were predicted and their expression in CSCC and adjacent tissues was evaluated. The targeting relationship was analyzed by dual-luciferase assays. Finally, rescue experiments were conducted. Results miR-214 was reduced in CSCC tissues and cells, and the survival of patients harboring overexpression of miR-214 was higher. miR-214 restoration increased CSCC cell apoptosis, while decreased proliferative, invasive and migratory activities. miR-214 interacted with vascular endothelial growth factor A (VEGFA) and B-cell CLL/lymphoma 2 (Bcl-2). VEGFA and Bcl-2, overexpressed in CSCC tissues and cells, were negatively correlated with miR-214. Moreover, VEGFA and Bcl-2 overexpression reversed the anti-tumor phenotype of miR-214 on CSCC cells. miR-214 disrupted the Wnt/β-catenin pathway through VEGFA and Bcl-2 in the CSCC cells. Conclusion Our data demonstrates that miR-214 exerts a suppressing role in CSCC. The discovery of novel targets such as miR-214 and VEGFA/Bcl-2 may facilitate the development of therapeutic options.

Angiogenesis in cancer

2012 ◽  
Vol 03 (04) ◽  
pp. 149-158
Author(s):  
M. Poettler ◽  
G. W. Prager
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Therapeutic Interventions ◽  
Cancer Development ◽  
Vascular Endothelial ◽  
Malignant Growth ◽  
Pharmacological Agents ◽  
Limited Efficacy ◽  
Novel Targets ◽  
Endothelial Growth Factor

SummaryEtiological concepts on cancer development, malignant growth and tumour propagation have undergone a revolutionary development during recent years: Among other aspects, the discovery of angiogenesis - the growth of new blood vessels from pre-existing vasculature - as a key element in the pathogenesis of malignancy has opened an abundance of biologic insights and subsequent therapeutic options, which have led to improved prognosis in many cancers including those originating from colon, lung, breast and kidney. Thereby, targeting the major pro-angiogenic stimulus vascular endothelial growth factor (VEGF) became the focus for therapeutic interventions. However, the use of VEGF-targeting drugs has been shown to be of limited efficacy, which might lie in the fact that tumor angiogenesis is mediated by a variety of different subcellular systems.This review focuses on the basic mechanisms involved in angiogenesis, which potentially represent novel targets for pharmacological agents in the treatment of malignancies.

Angiogenesis in cancer

2012 ◽  
Vol 32 (02) ◽  
pp. 105-114 ◽  
Author(s):  
M. Poettler ◽  
G. W. Prager
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Therapeutic Interventions ◽  
Cancer Development ◽  
Vascular Endothelial ◽  
Malignant Growth ◽  
Pharmacological Agents ◽  
Limited Efficacy ◽  
Novel Targets ◽  
Endothelial Growth Factor

SummaryEtiological concepts on cancer development, malignant growth and tumour propagation have undergone a revolutionary development during recent years: Among other aspects, the discovery of angiogenesis – the growth of new blood vessels from pre-existing vasculature – as a key element in the pathogenesis of malignancy has opened an abundance of biologic insights and subsequent therapeutic options, which have led to improved prognosis in many cancers including those originating from colon, lung, breast and kidney. Thereby, targeting the major pro-angiogenic stimulus vascular endothelial growth factor (VEGF) became the focus for therapeutic interventions. However, the use of VEGF-targeting drugs has been shown to be of limited efficacy, which might lie in the fact that tumor angiogenesis is mediated by a variety of different subcellular systems.This review focuses on the basic mechanisms involved in angiogenesis, which potentially represent novel targets for pharmacological agents in the treatment of malignancies.

scholarly journals Anti-vascular endothelial growth factor treatment for eye diseases

BMJ ◽  
2012 ◽  
Vol 344 (may01 2) ◽  
pp. e2970-e2970 ◽  
Author(s):  
N. Cheung ◽  
D. S. C. Lam ◽  
T. Y. Wong
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Eye Diseases ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Growth Factor Treatment

scholarly journals Angiogenesis during primate placentation in health and disease

Reproduction ◽  
2003 ◽  
pp. 569-577 ◽  
Author(s):  
C Wulff ◽  
M Weigand ◽  
R Kreienberg ◽  
HM Fraser
Keyword(s):  
Intrauterine Growth Retardation ◽  
Normal Development ◽  
Trophoblast Invasion ◽  
Vascular Endothelial ◽  
Angiogenic Growth Factors ◽  
Intrauterine Growth ◽  
Endothelial Cell Differentiation ◽  
Health And Disease ◽  
Endothelial Growth Factor ◽  
Proliferation And Invasion

Normal embryonic development is dependent upon a sufficient oxygen, nutrient and waste exchange through the placenta. In primates including humans, this exchange is attained by successful haemochorial placentation which requires the transformation of maternal intramyometrial spiral arterioles by trophoblast invasion to gain uteroplacental circulation, and establishment and maintenance of a competent fetoplacental vasculature. Thus, trophoblast and endothelial cell differentiation, proliferation and invasion occurring during placentation have to be tightly regulated. This review focuses on the diverse developmental steps during haemochorial placentation in humans and other primates and the possible involvement of angiogenic growth factors (vascular endothelial growth factor (VEGF) and angiopoietins (Ang)) in these processes, highlighting the importance of specific actions of angiogenic ligand-receptor pairs. It is hypothesized that VEGF/VEGF-R1 and Ang-1/Tie receptor 2 (Tie-2) may regulate trophoblast differentiation and invasion; VEGF/VEGF-R2 and Ang-1/Tie-2 may promote fetoplacental vascular development and stabilization; and Ang-2/Tie-2 may be involved in maternal vascular remodelling. The importance of a tight regulation of angiogenic factors and their endogenous antagonists for normal development of the placenta is demonstrated by failure of this system, resulting in abnormal placenta vascularization and trophoblast invasion associated with intrauterine growth retardation or pre-eclampsia.

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