Lymphangiogenesis in renal diseases: passive bystander or active participant?

2014 ◽  
Vol 16 ◽  
Author(s):  
Saleh Yazdani ◽  
Gerjan Navis ◽  
Jan-Luuk Hillebrands ◽  
Harry van Goor ◽  
Jacob van den Born
Keyword(s):  
Kidney Diseases ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Therapeutic Interventions ◽  
Lymph Vessel ◽  
Renal Diseases ◽  
Tissue Remodelling ◽  
The Past ◽  
Lymphatic Vasculature ◽  
Fibrotic Disorders

Lymphatic vessels (LVs) are involved in a number of physiological and pathophysiological processes such as fluid homoeostasis, immune surveillance, and resolution of inflammation and wound healing. Lymphangiogenesis, the outgrowth of existing LVs and the formation of new ones, has received increasing attention over the past decade on account of its prominence in organ physiology and pathology, which has been enabled by the development of specific tools to study lymph vessel functions. Several studies have been devoted to renal lymphatic vasculature and lymphangiogenesis in kidney diseases, such as chronic renal transplant dysfunction, primary renal fibrotic disorders, proteinuria, diabetic nephropathy and renal inflammation. This review describes the most recent findings on lymphangiogenesis, with a specific focus on renal lymphangiogenesis and its impact on renal diseases. We suggest renal lymphatics as a possible target for therapeutic interventions in renal medicine to dampen tubulointerstitial tissue remodelling and improve renal functioning.

scholarly journals Long noncoding RNAs in renal diseases

ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Minghui Liu ◽  
Jie Ren
Keyword(s):  
Gene Regulation ◽  
Kidney Diseases ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Renal Diseases ◽  
Malignant Cells ◽  
Transcriptional Noise ◽  
The Past ◽  
Eukaryotic Gene ◽  
Eukaryotic Gene Regulation

AbstractLong noncoding RNAs (lncRNAs) play critical roles in eukaryotic gene regulation and diseases, rather than being merely transcriptional “noise”. Over the past decade, the study of lncRNAs has emerged as a burgeoning field of research and expanded our knowledge of their functions and underlining mechanisms in both normal and malignant cells. However, lncRNAs are still one of the least understood groups of transcripts. Here, we review the classifications and functions of lncRNAs and their roles in renal diseases. This review will provide insights into the roles of lncRNAs in pathogenesis, diagnosis and therapeutics of renal diseases and indications of lncRNAs as potential targets for the treatment of kidney diseases.

Intravital two-photon microscopy of lymphatic vessel development and function using a transgenic Prox1 promoter-directed mOrange2 reporter mouse

2011 ◽  
Vol 39 (6) ◽  
pp. 1674-1681 ◽  
Author(s):  
René Hägerling ◽  
Cathrin Pollmann ◽  
Ludmila Kremer ◽  
Volker Andresen ◽  
Friedemann Kiefer
Keyword(s):  
Endothelial Cells ◽  
Fetal Development ◽  
Fluorescent Protein ◽  
Vascular System ◽  
Immune Surveillance ◽  
Adult Life ◽  
Lymphatic Vessels ◽  
Lymph Vessel ◽  
Adult Mice ◽  
Vessel Growth

Lymphatic vessels, the second vascular system of higher vertebrates, are indispensable for fluid tissue homoeostasis, dietary fat resorption and immune surveillance. Not only are lymphatic vessels formed during fetal development, when the lymphatic endothelium differentiates and separates from blood endothelial cells, but also lymphangiogenesis occurs during adult life under conditions of inflammation, wound healing and tumour formation. Under all of these conditions, haemopoietic cells can exert instructive influences on lymph vessel growth and are essential for the vital separation of blood and lymphatic vessels. LECs (lymphatic endothelial cells) are characterized by expression of a number of unique genes that distinguish them from blood endothelium and can be utilized to drive reporter genes in a lymph endothelial-specific fashion. In the present paper, we describe the Prox1 (prospero homeobox protein 1) promoter-driven expression of the fluorescent protein mOrange2, which allows the specific intravital visualization of lymph vessel growth and behaviour during mouse fetal development and in adult mice.

scholarly journals Neuroinflammation creates an immune regulatory niche at the meningeal lymphatic vasculature near the cribriform plate.

2021 ◽  
Author(s):  
Zsuzsanna Fabry ◽  
Martin Hsu ◽  
Collin Laaker ◽  
Andy Madrid ◽  
Melinda Herbath ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Cribriform Plate ◽  
Autoimmune Encephalomyelitis ◽  
New Therapeutic Approaches ◽  
Unrestricted Access ◽  
Drain Fluid ◽  
Lymphatic Vasculature ◽  
And Function ◽  
The Brain

Abstract Meningeal lymphatic vessels residing in the dural layer above the sinuses of the brain, meninges at the base of the brain, and near the cribriform plate have all been shown to drain fluid, cells, and antigens. We have previously reported that meningeal lymphatics near the cribriform plate undergo VEGFR3-dependent lymphangiogenesis during experimental autoimmune encephalomyelitis (EAE) to facilitate excess drainage. Using single-cell RNA sequencing (scRNA-seq), we report that neuroinflammation changes the phenotype and function of cribriform plate lymphatic endothelial cells (cpLECs). Upregulation of genes involved in antigen presentation, adhesion to leukocytes, and immunoregulatory molecules were verified by flow cytometry and functional assays. The inflamed cpLECs retain dendritic cells and to lesser extent CD4 T cells, creating an immune-regulatory niche that represents a previously underappreciated interface in the regulation of neuroinflammation. Additionally, the discontinuity of the arachnoid membrane near cpLECs provides unrestricted access to the cerebrospinal fluid (CSF) for immune surveillance. These findings may lead to new therapeutic approaches to neuroinflammatory diseases.

scholarly journals New insights about the lymphatic vasculature in cardiovascular diseases

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1811 ◽  
Author(s):  
Xiaolei Liu ◽  
Guillermo Oliver
Keyword(s):  
Blood Vessels ◽  
Cardiac Tissue ◽  
Lymphatic Vessels ◽  
Tissue Fluid ◽  
Major Focus ◽  
The Past ◽  
Growing Body ◽  
Lymphatic Vasculature ◽  
Coronary Blood Vessels ◽  
And Function

The heart contains a complex network of blood and lymphatic vessels. The coronary blood vessels provide the cardiac tissue with oxygen and nutrients and have been the major focus of research for the past few decades. Cardiac lymphatic vessels, which consist of lymphatic capillaries and collecting lymphatic vessels covering all layers of the heart, transport excess fluid from the interstitium and play important roles in maintaining tissue fluid balance. Unlike for the coronary blood vessels, until a few years ago, not much information was available on the origin and function of the cardiac-associated lymphatic vasculature. A growing body of evidence indicates that cardiac lymphatic vessels (lymphatics) may serve as a therapeutic cardiovascular target.

Truth Matters: Cognitive Integrity as an Intervention for Self-Deception

2017 ◽  
Author(s):  
Eugenia Isabel Gorlin ◽  
Michael W. Otto
Keyword(s):  
Decision Making ◽  
Problem Solving ◽  
Autonomous Agents ◽  
Therapeutic Interventions ◽  
Empirical Validation ◽  
The Past ◽  
Adaptive Problem

To live well in the present, we take direction from the past. Yet, individuals may engage in a variety of behaviors that distort their past and current circumstances, reducing the likelihood of adaptive problem solving and decision making. In this article, we attend to self-deception as one such class of behaviors. Drawing upon research showing both the maladaptive consequences and self-perpetuating nature of self-deception, we propose that self-deception is an understudied risk and maintaining factor for psychopathology, and we introduce a “cognitive-integrity”-based approach that may hold promise for increasing the reach and effectiveness of our existing therapeutic interventions. Pending empirical validation of this theoretically-informed approach, we posit that patients may become more informed and autonomous agents in their own therapeutic growth by becoming more honest with themselves.

scholarly journals Efficient aortic lymphatic drainage is necessary for atherosclerosis regression induced by ezetimibe

2020 ◽  
Vol 6 (50) ◽  
pp. eabc2697
Author(s):  
Kim Pin Yeo ◽  
Hwee Ying Lim ◽  
Chung Hwee Thiam ◽  
Syaza Hazwany Azhar ◽  
Caris Tan ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
Lymphatic Drainage ◽  
Lymphatic Transport ◽  
Atherosclerotic Plaques ◽  
Tissue Fluid ◽  
Atherosclerosis Progression ◽  
Lymphatic Vasculature ◽  
Lesion Regression ◽  
Transport Of Macromolecules

A functional lymphatic vasculature is essential for tissue fluid homeostasis, immunity, and lipid clearance. Although atherosclerosis has been linked to adventitial lymphangiogenesis, the functionality of aortic lymphatic vessels draining the diseased aorta has never been assessed and the role of lymphatic drainage in atherogenesis is not well understood. We develop a method to measure aortic lymphatic transport of macromolecules and show that it is impaired during atherosclerosis progression, whereas it is ameliorated during lesion regression induced by ezetimibe. Disruption of aortic lymph flow by lymphatic ligation promotes adventitial inflammation and development of atherosclerotic plaque in hypercholesterolemic mice and inhibits ezetimibe-induced atherosclerosis regression. Thus, progression of atherosclerotic plaques may result not only from increased entry of atherogenic factors into the arterial wall but also from reduced lymphatic clearance of these factors as a result of aortic lymph stasis. Our findings suggest that promoting lymphatic drainage might be effective for treating atherosclerosis.

scholarly journals Vascular endothelial cell specification in health and disease

Angiogenesis ◽  
2021 ◽  
Author(s):  
Corina Marziano ◽  
Gael Genet ◽  
Karen K. Hirschi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Current Knowledge ◽  
Vascular Malformations ◽  
Immune Surveillance ◽  
Vascular Endothelial Cell ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
The Body ◽  
Vascular Networks

AbstractThere are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.

scholarly journals Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xudong Zhu ◽  
Zhiyang Chen ◽  
Weiyan Shen ◽  
Gang Huang ◽  
John M. Sedivy ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cellular Response ◽  
State Of The Art ◽  
Cell Senescence ◽  
Therapeutic Interventions ◽  
Cell Fate Decision ◽  
The Past ◽  
Fate Decision ◽  
The Individual ◽  
Remarkable Progress

AbstractRemarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing. Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli, representing current hotspots as they not only (re-)shape the individual cell identity, but also involve in cell fate decision. This review focuses on the present findings and emerging concepts in epigenetic, inflammatory, and metabolic regulations and the consequences of the ageing process. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms, using state-of-the-art techniques are also discussed.

scholarly journals Mechanisms and cell lineages in lymphatic vascular development

Angiogenesis ◽  
2021 ◽  
Author(s):  
Daniyal J. Jafree ◽  
David A. Long ◽  
Peter J. Scambler ◽  
Christiana Ruhrberg
Keyword(s):  
Emerging Technologies ◽  
Vascular Development ◽  
Lymphatic Vessels ◽  
Experimental Techniques ◽  
Knowledge Gaps ◽  
Cellular Mechanisms ◽  
Cell Lineages ◽  
Lymphatic Vasculature ◽  
Lymphatic Development ◽  
Health And Disease

AbstractLymphatic vessels have critical roles in both health and disease and their study is a rapidly evolving area of vascular biology. The consensus on how the first lymphatic vessels arise in the developing embryo has recently shifted. Originally, they were thought to solely derive by sprouting from veins. Since then, several studies have uncovered novel cellular mechanisms and a diversity of contributing cell lineages in the formation of organ lymphatic vasculature. Here, we review the key mechanisms and cell lineages contributing to lymphatic development, discuss the advantages and limitations of experimental techniques used for their study and highlight remaining knowledge gaps that require urgent attention. Emerging technologies should accelerate our understanding of how lymphatic vessels develop normally and how they contribute to disease.

scholarly journals Beyond a Passive Conduit: Implications of Lymphatic Biology for Kidney Diseases

2020 ◽  
Vol 31 (6) ◽  
pp. 1178-1190 ◽  
Author(s):  
Daniyal J. Jafree ◽  
David A. Long
Keyword(s):  
Kidney Disease ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Transplant Rejection ◽  
Lymphatic Vessels ◽  
Renal Physiology ◽  
Clear Fluid ◽  
Adult Kidney ◽  
And Function ◽  
Development Structure

The kidney contains a network of lymphatic vessels that clear fluid, small molecules, and cells from the renal interstitium. Through modulating immune responses and via crosstalk with surrounding renal cells, lymphatic vessels have been implicated in the progression and maintenance of kidney disease. In this Review, we provide an overview of the development, structure, and function of lymphatic vessels in the healthy adult kidney. We then highlight the contributions of lymphatic vessels to multiple forms of renal pathology, emphasizing CKD, transplant rejection, and polycystic kidney disease and discuss strategies to target renal lymphatics using genetic and pharmacologic approaches. Overall, we argue the case for lymphatics playing a fundamental role in renal physiology and pathology and treatments modulating these vessels having therapeutic potential across the spectrum of kidney disease.

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