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Glomerular endothelium

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https://www.readbyqxmd.com/read/29026082/targeted-delivery-of-celastrol-to-mesangial-cells-is-effective-against-mesangioproliferative-glomerulonephritis
#1
Ling Guo, Shi Luo, Zhengwu Du, Meiling Zhou, Peiwen Li, Yao Fu, Xun Sun, Yuan Huang, Zhirong Zhang
Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29018490/the-promotion-of-nephropathy-by-porphyromonas-gingivalis-lipopolysaccharide-via-toll-like-receptors
#2
Koichiro Kajiwara, Shunsuke Takata, Thao T To, Kenyo Takara, Yuji Hatakeyama, Sachio Tamaoki, Richard Peters Darveau, Hiroyuki Ishikawa, Yoshihiko Sawa
BACKGROUND: Recently, we reported that toll-like receptor (TLR)2 and TLR4 localized on the glomerular endothelium in the glomeruli of streptozotocin (STZ)-induced type 1 diabetic mice and high fat diet feed-induced type 2 diabetic mice, and that periodontal pathogen Porphyromonas gingivalis LPS (Pg-LPS) administration lowered the survival rate of diabetic mice. The present study aims to examine the effect of TLR4 blocking on the suppression of Pg-LPS-induced diabetic nephropathy. METHODS: The survival rate and morphological/biochemical features for streptozotocin-induced diabetic mice with Pg-LPS and TLR4 blocker eritoran administration were investigated by reporter gene assay, urine and blood analysis, immunohistochemistry, and real time-PCR...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28916834/ultrastructural-characterization-of-the-glomerulopathy-in-alport-mice-by-helium-ion-scanning-microscopy-him
#3
Kenji Tsuji, Hani Suleiman, Jeffrey H Miner, James M Daley, Diane E Capen, Teodor G Păunescu, Hua A Jenny Lu
The glomerulus exercises its filtration barrier function by establishing a complex filtration apparatus consisting of podocyte foot processes, glomerular basement membrane and endothelial cells. Disruption of any component of the glomerular filtration barrier leads to glomerular dysfunction, frequently manifested as proteinuria. Ultrastructural studies of the glomerulus by transmission electron microscopy (TEM) and conventional scanning electron microscopy (SEM) have been routinely used to identify and classify various glomerular diseases...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28894214/the-novel-compound-sul-121-preserves-endothelial-function-and-inhibits-progression-of-kidney-damage-in-type-2-diabetes-mellitus-in-mice
#4
S P H Lambooy, A Bidadkosh, D Nakladal, A van Buiten, R A T Girgis, A C van der Graaf, T J Wiedenmann, R A Koster, P Vogelaar, H Buikema, R H Henning, L E Deelman
Diabetic nephropathy is still a common complication of type 2 diabetes mellitus (T2DM) and improvement of endothelial dysfunction (ED) and inhibition of reactive oxygen species (ROS) are considered important targets for new therapies. Recently, we developed a new class of compounds (Sul compounds) which inhibit mitochondrial ROS production. Here, we tested the therapeutic effects of Sul-121 on ED and kidney damage in experimental T2DM. Diabetic db/db and lean mice were implanted with osmotic pumps delivering Sul-121 (2...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865030/drebrin-in-renal-glomeruli
#5
Wiebke K Ludwig-Peitsch
The central function of renal glomeruli is plasma ultrafiltration for primary urine production. The glomerular filtration barrier consists of a fenestrated endothelium, the glomerular basement membrane and podocytes, mesenchymal-like cells with actin filament-rich protrusions, the "foot processes." Their architecture and function are maintained and regulated by actin and several actin-binding proteins, mutations of which can be causative of glomerular diseases. Since initial immunostaining experiments had demonstrated intense drebrin reactions in renal glomeruli, the distribution of this protein was studied in detail in the kidneys of diverse mammalian species...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28846193/the-endothelial-glycocalyx-in-health-and-kidney-disease-rising-star-or-false-dawn
#6
REVIEW
Hui Liew, Matthew A Roberts, Robert MacGinley, Lawrence P McMahon
The endothelial glycocalyx is a layer comprised of proteins and carbohydrates on the luminal surface of vascular endothelial cells, thought to have an important role in the health and function of the endothelium. Disrupted by various pathophysiological conditions and linked with clinical outcomes, it is increasingly recognised as an early indicator of endothelial injury and a potential marker of vascular injury. In this review, we discuss current methods of assessment (including novel optical approaches), evidence for its use as a marker of vascular disease and its potential role in relation to microalbuminuria and glomerular endothelial dysfunction...
August 28, 2017: Nephrology
https://www.readbyqxmd.com/read/28835895/antiangiogenic-therapy-for-diabetic-nephropathy
#7
REVIEW
Katsuyuki Tanabe, Yohei Maeshima, Yasufumi Sato, Jun Wada
Angiogenesis has been shown to be a potential therapeutic target for early stages of diabetic nephropathy in a number of animal experiments. Vascular endothelial growth factor (VEGF) is the main mediator for abnormal angiogenesis in diabetic glomeruli. Although beneficial effects of anti-VEGF antibodies have previously been demonstrated in diabetic animal experiments, recent basic and clinical evidence has revealed that the blockade of VEGF signaling resulted in proteinuria and renal thrombotic microangiopathy, suggesting the importance of maintaining normal levels of VEGF in the kidneys...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28814739/re-characterization-of-the-glomerulopathy-in-cd2ap-deficient-mice-by-high-resolution-helium-ion-scanning-microscopy
#8
Kenji Tsuji, Teodor G Păunescu, Hani Suleiman, Dongping Xie, Fahmy A Mamuya, Jeffrey H Miner, Hua A Jenny Lu
Helium ion scanning microscopy (HIM) is a novel technology that directly visualizes the cell surface ultrastructure without surface coating. Despite its very high resolution, it has not been applied extensively to study biological or pathology samples. Here we report the application of this powerful technology to examine the three-dimensional ultrastructural characteristics of proteinuric glomerulopathy in mice with CD2-associated protein (CD2AP) deficiency. HIM revealed the serial alteration of glomerular features including effacement and disorganization of the slit diaphragm, followed by foot process disappearance, flattening and fusion of major processes, and eventual transformation into a podocyte sheet as the disease progressed...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775003/interference-with-gs%C3%AE-coupled-receptor-signaling-in-renin-producing-cells-leads-to-renal-endothelial-damage
#9
Peter Lachmann, Linda Hickmann, Anne Steglich, Moath Al-Mekhlafi, Michael Gerlach, Niels Jetschin, Steffen Jahn, Brigitte Hamann, Monika Wnuk, Kirsten Madsen, Valentin Djonov, Min Chen, Lee S Weinstein, Bernd Hohenstein, Christian P M Hugo, Vladimir T Todorov
Intracellular cAMP, the production of which is catalyzed by the α-subunit of the stimulatory G protein (Gsα), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gsα in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gsα-deficient animals. Progressive albuminuria occurred in Gsα-deficient mice...
August 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28774335/a-comparative-study-on-the-efficacy-of-a-retrograde-perfusion-technique-and-an-antegrade-perfusion-technique-for-donor-kidney-recovery-in-transplantation-in-pigs
#10
Xiuwu Han, Xuhui Zhu, Tao Li, Yansheng Li, Hui Shan, Peng Zhang, Bulang He
BACKGROUND: Donor organ shortage is a significant problem in kidney transplantation. Improvement of perfusion techniques can increase the number of available organs. The aim of this study is to investigate the efficiency and safety of retrograde perfusion (RP) of kidney grafts during organ recovery after transplantation in pigs. METHODS: Ten pigs were divided into two groups, six in the study group for the RP technique and four in the control group for standard antegrade perfusion (AP)...
August 3, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28760115/a-model-of-acute-antibody-mediated-renal-allograft-rejection-in-the-sensitized-rata
#11
Sharmila Ramessur Chandran, William R Mulley, John Kanellis, David J Nikolic-Paterson, Frank Y Ma
OBJECTIVES: Antibody-mediated rejection in transplant recipients with preexisting donor-specific antibodies is a challenging clinical situation. However, we lack suitable animal models to study this scenario. The aim of this study was to develop an animal model of acute antibody-mediated rejection of renal allografts in sensitized recipients. MATERIALS AND METHODS: We used major histocompatibility complex class I and II incompatible rat strains (Dark Agouti RT1av1 and Lewis RT1l), which develop aggressive rejection...
July 31, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28759085/resveratrol-did-not-alter-blood-pressure-in-rats-with-nitric-oxide-synthase-inhibited-hypertension
#12
Mehmet Aydin, Buket Gungor, A Secil Akdur, Hakki Engin Aksulu, Coskun Silan, Ibrahim Susam, Ali Kemal Cabuk, Gizem Cabuk
BACKGROUND: Inhibition of nitric oxide synthase (NOS) is a well-known experimental model of hypertension (HT). It was shown that oxidative stress contributes to the pathogenesis of HT. Resveratrol is a potent anti-oxidant that is found in red grapes, peanuts and red wine. It improves the NO response and increases endothelial NOS expression, which causes endothelium-dependent vasorelaxation as well as renal vasodilation. We aimed to explore the effects of resveratrol on blood pressure, the water-salt balance and sodium excretion as a reflection of renal function in NOS-inhibited rat models...
May 2017: Cardiovascular Journal of Africa
https://www.readbyqxmd.com/read/28748185/novel-actions-of-growth-hormone-in-podocytes-implications-for-diabetic-nephropathy
#13
REVIEW
Dhanunjay Mukhi, Rajkishor Nishad, Ram K Menon, Anil Kumar Pasupulati
The kidney regulates water, electrolyte, and acid-base balance and thus maintains body homeostasis. The kidney's potential to ensure ultrafiltered and almost protein-free urine is compromised in various metabolic and hormonal disorders such as diabetes mellitus (DM). Diabetic nephropathy (DN) accounts for ~20-40% of mortality in DM. Proteinuria, a hallmark of renal glomerular diseases, indicates injury to the glomerular filtration barrier (GFB). The GFB is composed of glomerular endothelium, basement membrane, and podocytes...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28687535/endothelial-nf-%C3%AE%C2%BAb-blockade-abrogates-anca-induced-gn
#14
Mira Choi, Adrian Schreiber, Claudia Eulenberg-Gustavus, Claus Scheidereit, Jan Kamps, Ralph Kettritz
ANCA-associated vasculitis (AAV) is a highly inflammatory condition in which ANCA-activated neutrophils interact with the endothelium, resulting in necrotizing vasculitis. We tested the hypothesis that endothelial NF-κB mediates necrotizing crescentic GN (NCGN) and provides a specific treatment target. Reanalysis of kidneys from previously examined murine NCGN disease models revealed NF-κB activation in affected kidneys, mostly as a p50/p65 heterodimer, and increased renal expression of NF-κB-dependent tumor necrosis factor α (TNF-α)...
July 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28685678/glomerular-endothelium-and-its-impact-on-glomerular-filtration-barrier-in-diabetes-are-the-gaps-still-illusive
#15
Joseph Fomusi Ndisang
BACKGROUND: Glomerular capillaries are lined with highly specialized fenestrated endothelium which are primarily responsible to regulate high flux filtration of fluid and small solutes. During filtration, plasma passes through the fenestrated endothelium and basement membrane before it reaches the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocytes. METHODS: A PubMed search was done for recent articles on components of the glomerular filtration barrier such as glomerular endothelial cells, podocytes and glomerular basement membrane, and the effect of diabetes on these structures...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28656379/physiology-and-pathophysiology-of-the-plasminogen-system-in-the-kidney
#16
REVIEW
Per Svenningsen, Gitte Rye Hinrichs, Rikke Zachar, Rikke Ydegaard, Boye L Jensen
The plasminogen system is important for fibrinolysis in addition to tissue remodeling and inflammation with significance for kidney disease. The system consists of the circulating zymogen plasminogen (Plg) and the tissue- and urokinase-type plasminogen activators, tPA and uPA, expressed in the glomeruli, endothelium and tubular epithelium, respectively, and the inhibitors α2-antiplasmin and plasminogen activator inhibitor-type1, PAI-1. Plasminogen is activated by surface receptors, some with renal expression: urokinase-type plasminogen activator receptor (uPAR), plasminogen receptor KT (Plg-RKT), and tPA, most evident in the endothelium...
June 27, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28653860/gadolinium-deposition-in-human-brain-tissues-after-contrast-enhanced-mr-imaging-in-adult-patients-without-intracranial-abnormalities
#17
Robert J McDonald, Jennifer S McDonald, David F Kallmes, Mark E Jentoft, Michael A Paolini, David L Murray, Eric E Williamson, Laurence J Eckel
Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group)...
November 2017: Radiology
https://www.readbyqxmd.com/read/28551807/prohibitin-signaling-at-the-kidney-filtration-barrier
#18
REVIEW
Christina Ising, Paul T Brinkkoetter
The kidney filtration barrier consists of three well-defined anatomic layers comprising a fenestrated endothelium, the glomerular basement membrane (GBM) and glomerular epithelial cells, the podocytes. Podocytes are post-mitotic and terminally differentiated cells with primary and secondary processes. The latter are connected by a unique cell-cell contact, the slit diaphragm. Podocytes maintain the GBM and seal the kidney filtration barrier to prevent the onset of proteinuria. Loss of prohibitin-1/2 (PHB1/2) in podocytes results not only in a disturbed mitochondrial structure but also in an increased insulin/IGF-1 signaling leading to mTOR activation and a detrimental metabolic switch...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28542220/expression-of-receptor-type-protein-tyrosine-phosphatase-in-developing-and-adult-renal-vasculature
#19
Keiko Takahashi, Rachel Kim, Colette Lauhan, Yuna Park, Nghiep G Nguyen, Dietmar Vestweber, Melissa G Dominguez, David M Valenzuela, Andrew J Murphy, George D Yancopoulos, Nicholas W Gale, Takamune Takahashi
Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems...
2017: PloS One
https://www.readbyqxmd.com/read/28495931/neutrophil-extracellular-traps-drive-endothelial-to-mesenchymal-transition
#20
Elmar Pieterse, Nils Rother, Marjolein Garsen, Julia M Hofstra, Simon C Satchell, Markus Hoffmann, Markus A Loeven, Hanneke K Knaapen, Olivier W H van der Heijden, Jo H M Berden, Luuk B Hilbrands, Johan van der Vlag
OBJECTIVE: An excessive release and impaired degradation of neutrophil extracellular traps (NETs) leads to the continuous exposure of NETs to the endothelium in a variety of hematologic and autoimmune disorders, including lupus nephritis. This study aims to unravel the mechanisms through which NETs jeopardize vascular integrity. APPROACH AND RESULTS: Microvascular and macrovascular endothelial cells were exposed to NETs, and subsequent effects on endothelial integrity and function were determined in vitro and in vivo...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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