Endothelin axis induces metalloproteinase activation and invasiveness in human lymphatic endothelial cellsThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (8) ◽  
pp. 782-787 ◽  
Author(s):  
Francesca Spinella ◽  
Valentina Caprara ◽  
Emirena Garrafa ◽  
Valeriana Di Castro ◽  
Laura Rosanò ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Molecular Mechanisms ◽  
Proteolytic Enzymes ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cells ◽  
Special Issue ◽  
Dye Transport ◽  
Specific Antagonist ◽  
Endothelin B ◽  
Selection Of

The molecular mechanisms involved in lymphangiogenesis were unknown until recently. We previously demonstrated that the endothelin-1 (ET-1) axis stimulates lymphatic endothelial cells (LEC) and lymphatic vessels to grow and invade. Here we further investigated the effect of ET-1 on lymphatic vessels and evaluated whether ET-1 actions result in the functional activation of lymphangiogenesis. Using highly purified human LEC, characterized for the expression of ET-1 axis members by quantitative real-time PCR, we found that the endothelin B receptor (ETB), upon activation by ET-1, induced matrix-metalloproteinase activation, demonstrating that ET-1 influenced the activity of the proteolytic enzymes required for LEC invasion. Functional assays performed by using intradermal lymphangiography demonstrated that ET-1 promoted the formation of lymphatic vessels and that these vessels were capable of lymphatic flow. ETB blockade with the specific antagonist BQ788 inhibited matrix-metalloproteinase activation and dye transport within the lymphatic vessels, demonstrating that ETB is involved in the regulation of the growth of and in the formation of functional vessels upon activation by ET-1. Our results suggest that ET-1 is a lymphangiogenic mediator and that targeting pharmacologically ETB may be therapeutically exploited in a variety of diseases, including cancer.

scholarly journals Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress

2016 ◽  
Vol 13 (125) ◽  
pp. 20160823 ◽  
Author(s):  
Vinay N. Surya ◽  
Eleftheria Michalaki ◽  
Eva Y. Huang ◽  
Gerald G. Fuller ◽  
Alexander R. Dunn
Keyword(s):  
Endothelial Cells ◽  
Fluid Flow ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Lymphatic Vessels ◽  
Upstream Migration ◽  
Lymphatic Endothelial Cells ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

The endothelial cells that line blood and lymphatic vessels undergo complex, collective migration and rearrangement processes during embryonic development, and are known to be exquisitely responsive to fluid flow. At present, the molecular mechanisms by which endothelial cells sense fluid flow remain incompletely understood. Here, we report that both the G-protein-coupled receptor sphingosine 1-phosphate receptor 1 (S1PR1) and its ligand sphingosine 1-phosphate (S1P) are required for collective upstream migration of human lymphatic microvascular endothelial cells in an in vitro setting. These findings are consistent with a model in which signalling via S1P and S1PR1 are integral components in the response of lymphatic endothelial cells to the stimulus provided by fluid flow.

scholarly journals Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-κB and Prox1

Blood ◽  
2010 ◽  
Vol 115 (2) ◽  
pp. 418-429 ◽  
Author(s):  
Michael J. Flister ◽  
Andrew Wilber ◽  
Kelly L. Hall ◽  
Caname Iwata ◽  
Kohei Miyazono ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Lymphatic Vessels ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Lymphatic Endothelial Cells ◽  
Inflammatory Stimuli ◽  
And Migration

Abstract The concept of inflammation-induced lymphangiogenesis (ie, formation of new lymphatic vessels) has long been recognized, but the molecular mechanisms remained largely unknown. The 2 primary mediators of lymphangiogenesis are vascular endothelial growth factor receptor-3 (VEGFR-3) and Prox1. The key factors that regulate inflammation-induced transcription are members of the nuclear factor-kappaB (NF-κB) family; however, the role of NF-κB in regulation of lymphatic-specific genes has not been defined. Here, we identified VEGFR-3 and Prox1 as downstream targets of the NF-κB pathway. In vivo time-course analysis of inflammation-induced lymphangiogenesis showed activation of NF-κB followed by sequential up-regulation of Prox1 and VEGFR-3 that preceded lymphangiogenesis by 4 and 2 days, respectively. Activation of NF-κB by inflammatory stimuli also elevated Prox1 and VEGFR-3 expression in cultured lymphatic endothelial cells, resulting in increased proliferation and migration. We also show that Prox1 synergizes with the p50 of NF-κB to control VEGFR-3 expression. Collectively, our findings suggest that induction of the NF-κB pathway by inflammatory stimuli activates Prox1, and both NF-κB and Prox1 activate the VEGFR-3 promoter leading to increased receptor expression in lymphatic endothelial cells. This, in turn, enhances the responsiveness of preexisting lymphatic endothelium to VEGFR-3 binding factors, VEGF-C and VEGF-D, ultimately resulting in robust lymphangiogenesis.

Endothelial cell-specific ETB receptor knockout: autoradiographic and histological characterisation and crucial role in the clearance of endothelin-1This article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (6) ◽  
pp. 644-651 ◽  
Author(s):  
N.F. Kelland ◽  
R.E. Kuc ◽  
D.L. McLean ◽  
A. Azfer ◽  
A.J. Bagnall ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Genetic Mutation ◽  
Special Issue ◽  
Rt Pcr ◽  
Similar Extent ◽  
Relative Contribution ◽  
Liver And Kidney ◽  
Etb Receptor ◽  
Endothelin B ◽  
Selection Of

Inactivation of endothelin B receptors (ETB), either through selective pharmacological antagonism or genetic mutation, increases the circulating concentration of endothelin-1 (ET-1), suggesting ETB plays an important role in clearance of this peptide. However, the cellular site of ETB-mediated clearance has not yet been determined. We have used a novel mouse model of endothelial cell-specific knockout (KO) of ETB (EC ETB–/–) to evaluate the relative contribution of EC-ETB to the clearance of ET-1. Phenotypic evidence of EC-specific ETB KO was confirmed by immunocytochemistry and autoradiography. Binding of the radiolabelled selective ETB ligand BQ3020 was significantly and selectively decreased in EC-rich tissues of EC ETB–/– mice, including the lung, liver, and kidney. By contrast, ETA binding was unaltered. RT-PCR confirmed equal expression of ET-1 in tissue from EC ETB–/– mice and controls, despite increased concentration of plasma ET-1 in EC ETB–/–. Clearance of an intravenous bolus of [125I]ET-1 was impaired in EC ETB–/– mice. Pretreatment with the selective ETB antagonist A192621 impaired [125I]ET-1 clearance in control animals to a similar extent, but did not further impair clearance in EC ETB–/– mice. These studies suggest that EC-ETB are largely responsible for the clearance of ET-1 from the circulation.

Introduction: Affixes and bases

2011 ◽  
Vol 4 (2) ◽  
pp. 161-168
Author(s):  
Stela Manova
Keyword(s):  
Special Issue ◽  
Affix Order ◽  
Selection Of ◽  
Affix Ordering

This special issue includes a selection of papers presented at the 2nd Vienna Workshop on Affix Order held in Vienna, Austria on June 4–5, 2009. The workshop was in honor of Wolfgang U. Dressler on the occasion of his 70th birthday. However, this special issue differs from the classical Festschrift dedicated to a renowned scholar and is ‘more special’ in two respects at least: 1) not all authors are Dressler's friends and colleagues, some of them are only indirectly related to him, through his students; and 2) since the papers were presented at a topic-oriented workshop, they are thematically uniform. In other words, this special issue is a kind of scientific genealogy in terms of affix ordering. Thus, the title Affixes and bases should be understood in two ways: literally – affixes and bases as linguistic notions, and metaphorically – affixes and bases as linguists related directly and indirectly to a prominent base: Wolfgang U. Dressler.

scholarly journals The Telocytes in the Subepicardial Niche

2019 ◽  
Vol 9 (8) ◽  
pp. 1615 ◽  
Author(s):  
Cristian Bogdan Iancu ◽  
Mugurel Constantin Rusu ◽  
Laurenţiu Mogoantă ◽  
Sorin Hostiuc ◽  
Oana Daniela Toader
Keyword(s):  
Stromal Cells ◽  
Lymphatic Vessels ◽  
Growth Factor Receptor ◽  
Immunohistochemical Method ◽  
Lymphatic Endothelial Cells ◽  
Cell Type ◽  
Ki 67 ◽  
Epicardial Cells ◽  
Immunohistochemical Evidence ◽  
Unique Cell

A great interest has developed over the last several years in research on interstitial Cajal-like cells (ICLCs), later renamed to telocytes (TCs). Such studies are restricted by diverse limitations. We aimed to critically review (sub)epicardial ICLCs/TCs and to bring forward supplemental immunohistochemical evidence on (sub)epicardial stromal niche inhabitants. We tested the epicardial expressions of CD117/c-kit, CD34, Cytokeratin 7 (CK7), Ki67, Platelet-Derived Growth Factor Receptor (PDGFR)-α and D2-40 in adult human cardiac samples. The mesothelial epicardial cells expressed D2-40, CK7, CD117/c-kit and PDGFR-α. Subepicardial D2-40-positive lymphatic vessels and isolated D2-40-positive and CK7-positive subepicardial cells were also found. Immediate submesothelial spindle-shaped cells expressed Ki-67. Submesothelial stromal cells and endothelial tubes were PDGFR-α-positive and CD34-positive. The expression of CD34 was pan-stromal, so a particular stromal cell type could not be distinguished. The stromal expression of CD117/c-kit was also noted. It seems that epicardial TCs could not be regarded as belonging to a unique cell type until (pre)lymphatic endothelial cells are inadequately excluded. Markers such as CD117/c-kit or CD34 seem to be improper for identifying TCs as a distinctive cell type. Care should be taken when using the immunohistochemical method and histological interpretations, as they may not produce accurate results.

tti2002: Introduction and Conference Overview

2003 ◽  
Vol 17 (1) ◽  
pp. 9-14 ◽  
Author(s):  
E. H. Robson
Keyword(s):  
Higher Education ◽  
Technology Transfer ◽  
Special Issue ◽  
International Convention ◽  
International Conference ◽  
Introductory Paper ◽  
Personal Reflections ◽  
Selection Of

This special issue of Industry and Higher Education is devoted to a selection of papers and reports from tti2002, an international conference on technology transfer and innovation held at the International Convention Centre, Birmingham, UK in July 2002. In this introductory paper, the author provides the context of the conference, summarizes the presentations given by invited speakers and offers personal reflections on the event.

scholarly journals Recent Advances in Kinase Drug Discovery Part I: The Editors’ Take

2021 ◽  
Vol 22 (14) ◽  
pp. 7560
Author(s):  
Julie A. Tucker ◽  
Mathew P. Martin
Keyword(s):  
Drug Discovery ◽  
Research Articles ◽  
Special Issue ◽  
Recent Advances ◽  
Enzyme Family ◽  
Selection Of

This special issue on Advances in Kinase Drug Discovery provides a selection of research articles and topical reviews covering all aspects of drug discovery targeting the phosphotransferase enzyme family [...]

scholarly journals Advances in the Molecular Mechanisms of Abscisic Acid and Gibberellins Functions in Plants

2021 ◽  
Vol 22 (11) ◽  
pp. 6080
Author(s):  
Víctor Quesada
Keyword(s):  
Abscisic Acid ◽  
Molecular Mechanisms ◽  
Original Research ◽  
Special Issue ◽  
Research Papers

In this special issue entitled, “Advances in the Molecular Mechanisms of Abscisic Acid and Gibberellins Functions in Plants”, eight articles are collected, with five reviews and three original research papers, which broadly cover different topics on the abscisic acid (ABA) field and, to a lesser extent, on gibberellins (GAs) research [...]

scholarly journals Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Mechanical Forces ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Development ◽  
And Function ◽  
The Impact

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.

scholarly journals Combining QTL Mapping and Gene Expression Analysis to Elucidate the Genetic Control of ‘Crumbly’ Fruit in Red Raspberry (Rubus idaeus L.)

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 794
Author(s):  
Luca M. Scolari ◽  
Robert D. Hancock ◽  
Pete E. Hedley ◽  
Jenny Morris ◽  
Kay Smith ◽  
...  
Keyword(s):  
Genetic Control ◽  
Developmental Disorder ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Microarray Experiment ◽  
Rubus Idaeus ◽  
Red Raspberry ◽  
Genotype By Sequencing ◽  
First Time ◽  
Selection Of

‘Crumbly’ fruit is a developmental disorder in raspberry that results in malformed and unsaleable fruits. For the first time, we define two distinct crumbly phenotypes as part of this work. A consistent crumbly fruit phenotype affecting the majority of fruits every season, which we refer to as crumbly fruit disorder (CFD) and a second phenotype where symptoms vary across seasons as malformed fruit disorder (MFD). Here, segregation of crumbly fruit of the MFD phenotype was examined in a full-sib family and three QTL (Quantitative Trait Loci) were identified on a high density GbS (Genotype by Sequencing) linkage map. This included a new QTL and more accurate location of two previously identified QTLs. A microarray experiment using normal and crumbly fruit at three different developmental stages identified several genes that were differentially expressed between the crumbly and non-crumbly phenotypes within the three QTL. Analysis of gene function highlighted the importance of processes that compromise ovule fertilization as triggers of crumbly fruit. These candidate genes provided insights regarding the molecular mechanisms involved in the genetic control of crumbly fruit in red raspberry. This study will contribute to new breeding strategies and diagnostics through the selection of molecular markers associated with the crumbly trait.

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