scholarly journals Podocyte endocytosis in the regulation of the glomerular filtration barrier

2015 ◽  
Vol 309 (5) ◽  
pp. F398-F405 ◽  
Author(s):  
Kazunori Inoue ◽  
Shuta Ishibe
Keyword(s):  
Glomerular Filtration ◽  
Critical Role ◽  
Vital Role ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Endocytic Machinery ◽  
Health And Disease ◽  
Models Of Disease ◽  
Genetic Mouse Models

Severe defects in the glomerular filtration barrier result in nephrotic syndrome, which is characterized by massive proteinuria. The podocyte, a specialized epithelial cell with interdigitating foot processes separated by a slit diaphragm, plays a vital role in regulating the passage of proteins from the capillary lumen to Bowman's space. Recent findings suggest a critical role for endocytosis in podocyte biology as highlighted by genetic mouse models of disease and human genetic mutations that result in the loss of the integrity of the glomerular filtration barrier. In vitro podocyte studies have also unraveled a plethora of constituents that are differentially internalized to maintain homeostasis. These observations provide a framework and impetus for understanding the precise regulation of podocyte endocytic machinery in both health and disease.

scholarly journals The critical role of Krüppel-like factors in kidney disease

2017 ◽  
Vol 312 (2) ◽  
pp. F259-F265 ◽  
Author(s):  
Sandeep K. Mallipattu ◽  
Chelsea C. Estrada ◽  
John C. He
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
Vital Role ◽  
Glomerular Filtration Barrier ◽  
Kidney Fibrosis ◽  
Physiological Processes ◽  
Filtration Barrier ◽  
And Function ◽  
Mammalian Embryonic Development

Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation to progression of kidney fibrosis. Seventeen members of the KLF family have been identified, and several have been well characterized in the kidney. Although they may share some overlap in their downstream targets, their structure and function remain distinct. This review highlights our current knowledge of KLFs in the kidney, which includes their pattern of expression and their function in regulating key biological processes. We will also critically examine the currently available literature on KLFs in the kidney and offer some key areas in need of further investigation.

scholarly journals Glomerular endothelial cell fenestrations: an integral component of the glomerular filtration barrier

2009 ◽  
Vol 296 (5) ◽  
pp. F947-F956 ◽  
Author(s):  
Simon C. Satchell ◽  
Filip Braet
Keyword(s):  
Endothelial Cell ◽  
Glomerular Filtration ◽  
In Vitro Models ◽  
Glomerular Injury ◽  
Glomerular Endothelial Cell ◽  
Glomerular Filtration Barrier ◽  
Therapeutic Implications ◽  
Filtration Barrier ◽  
Glomerular Development

Glomerular endothelial cell (GEnC) fenestrations are analogous to podocyte filtration slits, but their important contribution to the glomerular filtration barrier has not received corresponding attention. GEnC fenestrations are transcytoplasmic holes, specialized for their unique role as a prerequisite for filtration across the glomerular capillary wall. Glomerular filtration rate is dependent on the fractional area of the fenestrations and, through the glycocalyx they contain, GEnC fenestrations are important in restriction of protein passage. Hence, dysregulation of GEnC fenestrations may be associated with both renal failure and proteinuria, and the pathophysiological importance of GEnC fenestrations is well characterized in conditions such as preeclampsia. Recent evidence suggests a wider significance in repair of glomerular injury and in common, yet serious, conditions, including diabetic nephropathy. Study of endothelial cell fenestrations is challenging because of limited availability of suitable in vitro models and by the requirement for electron microscopy to image these sub-100-nm structures. However, extensive evidence, from glomerular development in rodents to in vitro studies in human GEnC, points to vascular endothelial growth factor (VEGF) as a key inducer of fenestrations. In systemic endothelial fenestrations, the intracellular pathways through which VEGF acts to induce fenestrations include a key role for the fenestral diaphragm protein plasmalemmal vesicle-associated protein-1 (PV-1). The role of PV-1 in GEnC is less clear, not least because of controversy over existence of GEnC fenestral diaphragms. In this article, the structure-function relationships of GEnC fenestrations will be evaluated in depth, their role in health and disease explored, and the outlook for future study and therapeutic implications of these peculiar structures will be approached.

scholarly journals “Zebrafishing” for Novel Genes Relevant to the Glomerular Filtration Barrier

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Nils Hanke ◽  
Lynne Staggs ◽  
Patricia Schroder ◽  
Jennifer Litteral ◽  
Susanne Fleig ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Barrier Function ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Glomerular Filtration Barrier ◽  
Novel Genes ◽  
Zebrafish Model ◽  
Filtration Barrier

Data for genes relevant to glomerular filtration barrier function or proteinuria is continually increasing in an era of microarrays, genome-wide association studies, and quantitative trait locus analysis. Researchers are limited by published literature searches to select the most relevant genes to investigate. High-throughput cell cultures and otherin vitrosystems ultimately need to demonstrate proof in anin vivomodel. Generating mammalian models for the genes of interest is costly and time intensive, and yields only a small number of test subjects. These models also have many pitfalls such as possible embryonic mortality and failure to generate phenotypes or generate nonkidney specific phenotypes. Here we describe anin vivozebrafish model as a simple vertebrate screening system to identify genes relevant to glomerular filtration barrier function. Using our technology, we are able to screen entirely novel genes in 4–6 weeks in hundreds of live test subjects at a fraction of the cost of a mammalian model. Our system produces consistent and reliable evidence for gene relevance in glomerular kidney disease; the results then provide merit for further analysis in mammalian models.

scholarly journals PD33-01 GLOMERULUS ON-A-CHIP AS A MODEL TO STUDY THE GLOMERULAR FILTRATION BARRIER IN VITRO

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Stefano Da Sacco ◽  
Paul Vulto ◽  
Jos Joore ◽  
Roger De Filippo ◽  
Laura Perin
Keyword(s):  
Glomerular Filtration ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier

scholarly journals A microphysiological system to investigate the pressure dependent filtration at an artificial glomerular kidney barrier

2019 ◽  
Vol 5 (1) ◽  
pp. 389-391
Author(s):  
Florian Schmieder ◽  
Stefan Behrens ◽  
Nina Reustle ◽  
Nathalie Franke ◽  
Frank Sonntag ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration ◽  
High Blood Pressure ◽  
Culture Media ◽  
Glomerular Filtration Barrier ◽  
Hypertonic Stress ◽  
Filtration Barrier ◽  
Micro Pump ◽  
Glomerular Barrier

AbstractChronic kidney disease (CKD) is a global health problem that affects around 11 to 13% of the world’s population and more than 18% of European citizens. Characteristic syndromes of CKD during all stages of the disease are proteinuria and ongoing glomerular dysfunction caused by cellular damages at the glomerular filtration barrier. While some rare cases of the disease are correlated to genetic depositions the majority of cases are caused by diabetes, glomerulosclerosis, high blood pressure and glomerulonephritis. Thus, recapitulating the interplay of high blood pressure and changes at the glomerular filtration barrier in vitro seems an adequate way to mimic CKD. Here we present a microphysiological system of the glomerular filter that is capable to simulate high blood pressure at the glomerular filtration barrier in vitro. It consists of a closed loop microfluidic circuit with an integrated pneumatically driven heart like micro pump that constantly circulates the cell culture media at the blood site of the glomerular barrier. The ThinCert™ insert could be reversibly integrated into a holder system that ensures the correct position of the insert within the microfluidic circuit. By using different modulations of the integrated pneumatic micro pump different physiological and pathophysiological conditions e.g. hypertonic stress, like in CKD, could be applied. The influence of hypertonic conditions on the filtration above the barrier was studied by changes of TEER values and measurement of the flux of fluorescent labelled albumin through the cellular barrier.

Reduced diffusion of charge-modified, conformationally intact anionic Ficoll relative to neutral Ficoll across the rat glomerular filtration barrier in vivo

2011 ◽  
Vol 301 (4) ◽  
pp. F708-F712 ◽  
Author(s):  
Josefin Axelsson ◽  
Kristinn Sverrisson ◽  
Anna Rippe ◽  
William Fissell ◽  
Bengt Rippe
Keyword(s):  
Glomerular Filtration ◽  
High Performance ◽  
Size Exclusion ◽  
Glomerular Filtration Barrier ◽  
Glomerular Permeability ◽  
Charge Effects ◽  
Filtration Barrier ◽  
A Charge

The glomerular filtration barrier (GFB) is commonly conceived as a negatively charged sieve to proteins. Recent studies, however, indicate that glomerular charge effects are small for anionic, carboxymethylated (CM) dextran vs. neutral dextran. Furthermore, two studies assessing the glomerular sieving coefficients (θ) for negative CM-Ficoll vs. native Ficoll have demonstrated an increased glomerular permeability for CM-Ficoll (Asgeirsson D, Venturoli D, Rippe B, Rippe C. Am J Physiol Renal Physiol 291: F1083–F1089, 2006; Guimarães M, Nikolovski J, Pratt L, Greive K, Comper W. Am Physiol Renal Physiol 285: F1118–F1124, 2003.). The CM-Ficoll used, however, showed a larger Stokes-Einstein radius ( ae) than neutral Ficoll, and it was proposed that the introduction of negative charges in the Ficoll molecule had made it more flexible and permeable. Recently, a negative FITC-labeled CM-Ficoll (CMI-Ficoll) was produced with a conformation identical to that of neutral FITC-Ficoll. Using these probes, we determined their θ:s in anesthetized Wistar rats (259 ± 2.5 g). After blood access had been achieved, the left ureter was cannulated for urine sampling. Either polysaccharide was infused (iv) together with a filtration marker, and urine and plasma were collected. Assessment of θ FITC-Ficoll was achieved by high-performance size-exclusion chromatography (HPSEC). CMI-Ficoll and native Ficoll had identical elugrams on the HPSEC. Diffusion of anionic Ficoll was significantly reduced compared with that of neutral Ficoll across the GFB for molecules of ae ∼20–35 Å, while there were no charge effects for Ficoll of ae = 35–80 Å. The data are consistent with a charge effect present in “small pores,” but not in “large pores,” of the GFB and mimicked those obtained for anionic membranes in vitro for the same probes.

scholarly journals Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk

2021 ◽  
Vol 12 ◽  
Author(s):  
Kerstin Ebefors ◽  
Emelie Lassén ◽  
Nanditha Anandakrishnan ◽  
Evren U. Azeloglu ◽  
Ilse S. Daehn
Keyword(s):  
Glomerular Filtration ◽  
Three Dimensional ◽  
New Wave ◽  
Glomerular Filtration Barrier ◽  
Outermost Layer ◽  
The Past ◽  
Filtration Barrier ◽  
Urine Production ◽  
Compact Cluster

The glomerulus is a compact cluster of capillaries responsible for blood filtration and initiating urine production in the renal nephrons. A trilaminar structure in the capillary wall forms the glomerular filtration barrier (GFB), composed of glycocalyx-enriched and fenestrated endothelial cells adhering to the glomerular basement membrane and specialized visceral epithelial cells, podocytes, forming the outermost layer with a molecular slit diaphragm between their interdigitating foot processes. The unique dynamic and selective nature of blood filtration to produce urine requires the functionality of each of the GFB components, and hence, mimicking the glomerular filter in vitro has been challenging, though critical for various research applications and drug screening. Research efforts in the past few years have transformed our understanding of the structure and multifaceted roles of the cells and their intricate crosstalk in development and disease pathogenesis. In this review, we present a new wave of technologies that include glomerulus-on-a-chip, three-dimensional microfluidic models, and organoids all promising to improve our understanding of glomerular biology and to enable the development of GFB-targeted therapies. Here, we also outline the challenges and the opportunities of these emerging biomimetic systems that aim to recapitulate the complex glomerular filter, and the evolving perspectives on the sophisticated repertoire of cellular signaling that comprise the glomerular milieu.

The podocyte in health and disease: insights from the mouse

2007 ◽  
Vol 112 (6) ◽  
pp. 325-335 ◽  
Author(s):  
Jean-Louis R. Michaud ◽  
Chris R. J. Kennedy
Keyword(s):  
Glomerular Filtration ◽  
Genetic Manipulation ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Form And Function ◽  
Filtration Barrier ◽  
Scientific Disciplines ◽  
Fenestrated Endothelium ◽  
Health And Disease ◽  
And Function

The glomerular filtration barrier consists of the fenestrated endothelium, the glomerular basement membrane and the terminally differentiated visceral epithelial cells known as podocytes. It is now widely accepted that damage to, or originating within, the podocytes is a key event that initiates progression towards sclerosis in many glomerular diseases. A wide variety of strategies have been employed by investigators from many scientific disciplines to study the podocyte. Although invaluable insights have accrued from conventional approaches, including cell culture and biochemical-based methods, many renal researchers continue to rely upon the mouse to address the form and function of the podocyte. This review summarizes how genetic manipulation in the mouse has advanced our understanding of the podocyte in relation to the maintenance of the glomerular filtration barrier in health and disease.

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