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.

scholarly journals Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans

2016 ◽  
Vol 40 (5) ◽  
pp. 819-830 ◽  
Author(s):  
Janina Müller-Deile ◽  
Finn Gellrich ◽  
Heiko Schenk ◽  
Patricia Schroder ◽  
Jenny Nyström ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Glomerular Filtration ◽  
Cell Types ◽  
Endothelial Damage ◽  
Micro Rna ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Glomerular Endothelial Cells ◽  
Apoptotic Pathways

Background: TGF-β is known as an important stress factor of podocytes in glomerular diseases. Apart from activation of direct pro-apoptotic pathways we wanted to analyze micro-RNA (miRs) driven regulation of components involved in the integrity of the glomerular filtration barrier induced by TGF-β. Since miR-143-3p (miR-143) is described as a TGF-β inducible miR in other cell types, we examined this specific miR and its ability to induce glomerular pathology. Methods: We analyzed miR-143 expression in cultured human podocytes after stimulation with TGF-β. We also microinjected zebrafish eggs with a miR-143 mimic or with morpholinos specific for its targets syndecan and versican and compared phenotype and proteinuria development. Results: We detected a time dependent, TGF-β inducible expression of miR-143 in human podocytes. Targets of miR-143 relevant in glomerular biology are syndecans and versican, which are known components of the glycocalyx. We found that syndecan 1 and 4 were predominantly expressed in podocytes while syndecan 3 was largely expressed in glomerular endothelial cells. Versican could be detected in both cell types. After injection of a miR-143 mimic in zebrafish larvae, syndecan 3, 4 and versican were significantly downregulated. Moreover, miR-143 overexpression or versican knockdown by morpholino caused loss of plasma proteins, edema, podocyte effacement and endothelial damage. In contrast, knockdown of syndecan 3 and syndecan 4 had no effects on glomerular filtration barrier. Conclusion: Expression of versican and syndecan isoforms is indispensable for proper barrier function. Podocyte-derived miR-143 is a mediator for paracrine and autocrine cross talk between podocytes and glomerular endothelial cells and can alter expression of glomerular glycocalyx proteins.

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.

Glomerular Endothelium and its Impact on Glomerular Filtration Barrier in Diabetes: Are the Gaps Still Illusive?

2018 ◽  
Vol 25 (13) ◽  
pp. 1525-1529 ◽  
Author(s):  
Joseph Fomusi Ndisang
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Healthy Individuals ◽  
Kidney Dysfunction ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Glomerular Endothelial Cells ◽  
Fenestrated Endothelium

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. Results and Conclusion: Generally, the onset of kidney dysfunction in many diabetic patients is characterized by albuminuria/proteinuria, a pathophysiological event triggered by several factors including; (i) endothelial activation and shading of glycocalyx, (ii) loss of endothelial cell function, (ii) re-uptake of albumin by podocyte through a scavenger receptors and (iv) rearrangement of podocyte cytoskeleton. Howeover, as podocyte effacement does not always lead to proteinuria, the dynamic interplay between all constituents of the glomerular filtration barrier including podocytes, endothelial cells and the basement membrane may be fundamental for the effective filtration in healthy individuals. Thus, a putative cross-talk amongst podocytes, endothelial cells and the basement membrane in the homeostasis of glomerular function is envisaged. Although, the exact nature of this cross-talk remains to be clearly elucidated, it is possible that the interaction between: (i) glomerular endothelial cells and podocytes, (ii) glomerular endothelial cells and glomerular basement membrane, (iii) podocytes and glomerular basement membrane, and (iv) the simultaneous interaction amongst the three components collectively underpin effective filtration in healthy individuals. A comprehensive understanding of these different interactions still remains elusive. The elucidation of these multifaceted interactions will set the stage for greater understanding of the pathophysiology of kidney dysfunction.

scholarly journals Understanding the Mechanisms of Proteinuria: Therapeutic Implications

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jorge E. Toblli ◽  
P. Bevione ◽  
F. Di Gennaro ◽  
L. Madalena ◽  
G. Cao ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Strong Predictor ◽  
Large Body ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Wide Range

A large body of evidence indicates that proteinuria is a strong predictor of morbidity, a cause of inflammation, oxidative stress and progression of chronic kidney disease, and development of cardiovascular disease. The processes that lead to proteinuria are complex and involve factors such as glomerular hemodynamic, tubular absorption, and diffusion gradients. Alterations in various different molecular pathways and interactions may lead to the identical clinical end points of proteinuria and chronic kidney disease. Glomerular diseases include a wide range of immune and nonimmune insults that may target and thus damage some components of the glomerular filtration barrier. In many of these conditions, the renal visceral epithelial cell (podocyte) responds to injury along defined pathways, which may explain the resultant clinical and histological changes. The recent discovery of the molecular components of the slit diaphragm, specialized structure of podocyte-podocyte interaction, has been a major breakthrough in understanding the crucial role of the epithelial layer of the glomerular barrier and the pathogenesis of proteinuria. Thispaper provides an overview and update on the structure and function of the glomerular filtration barrier and the pathogenesis of proteinuria, highlighting the role of the podocyte in this setting. In addition, current antiproteinuric therapeutic approaches are briefly commented.

scholarly journals Podocyte Autophagy in Homeostasis and Disease

2021 ◽  
Vol 10 (6) ◽  
pp. 1184
Author(s):  
Qisheng Lin ◽  
Khadija Banu ◽  
Zhaohui Ni ◽  
Jeremy S. Leventhal ◽  
Madhav C. Menon
Keyword(s):  
Glomerular Filtration ◽  
Functional Role ◽  
Specific Reference ◽  
Protective Mechanism ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Filtration Barrier ◽  
Cellular Autophagy ◽  
Survival Mechanisms

Autophagy is a protective mechanism that removes dysfunctional components and provides nutrition for cells. Podocytes are terminally differentiated specialized epithelial cells that wrap around the capillaries of the glomerular filtration barrier and show high autophagy level at the baseline. Here, we provide an overview of cellular autophagy and its regulation in homeostasis with specific reference to podocytes. We discuss recent data that have focused on the functional role and regulation of autophagy during podocyte injury in experimental and clinical glomerular diseases. A thorough understanding of podocyte autophagy could shed novel insights into podocyte survival mechanisms with injury and offer potential targets for novel therapeutics for glomerular disease.

scholarly journals Gangliosides in Podocyte Biology and Disease

2020 ◽  
Vol 21 (24) ◽  
pp. 9645
Author(s):  
Berkan Savas ◽  
Giuseppe Astarita ◽  
Massimo Aureli ◽  
Dil Sahali ◽  
Mario Ollero
Keyword(s):  
Sialic Acid ◽  
Glomerular Filtration ◽  
Cellular Component ◽  
Cellular Membranes ◽  
Glomerular Filtration Barrier ◽  
Cell Homeostasis ◽  
Multiple Functions ◽  
Filtration Barrier ◽  
Metabolic Precursors ◽  
And Function

Gangliosides constitute a subgroup of glycosphingolipids characterized by the presence of sialic acid residues in their structure. As constituents of cellular membranes, in particular of raft microdomains, they exert multiple functions, some of them capital in cell homeostasis. Their presence in cells is tightly regulated by a balanced expression and function of the enzymes responsible for their biosynthesis, ganglioside synthases, and their degradation, glycosidases. The dysregulation of their abundance results in rare and common diseases. In this review, we make a point on the relevance of gangliosides and some of their metabolic precursors, such as ceramides, in the function of podocytes, the main cellular component of the glomerular filtration barrier, as well as their implications in podocytopathies. The results presented in this review suggest the pertinence of clinical lipidomic studies targeting these metabolites.

Cell Biology of the Glomerular Podocyte

2003 ◽  
Vol 83 (1) ◽  
pp. 253-307 ◽  
Author(s):  
Hermann Pavenstädt ◽  
Wilhelm Kriz ◽  
Matthias Kretzler
Keyword(s):  
Glomerular Filtration ◽  
Cell Biology ◽  
Considerable Increase ◽  
Gene Products ◽  
Common Theme ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Selective Permeability ◽  
Filtration Barrier

Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

scholarly journals Adriamycin does not damage podocytes of zebrafish larvae

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242436
Author(s):  
Maximilian Schindler ◽  
Antje Blumenthal ◽  
Marcus Johannes Moeller ◽  
Karlhans Endlich ◽  
Nicole Endlich
Keyword(s):  
Glomerular Filtration ◽  
Rapid Development ◽  
Glomerular Injury ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Zebrafish Larvae ◽  
Filtration Barrier ◽  
Suitable Animal Model ◽  
Similar Phenotype

Podocytes are highly specialized epithelial cells that are essential for an intact glomerular filtration barrier in the kidney. Several glomerular diseases like focal segmental glomerulosclerosis (FSGS) are initially due to podocyte injury and loss. Since causative treatments for FSGS are not available until today, drug screening is of great relevance. In order to test a high number of drugs, FSGS needs to be reliably induced in a suitable animal model. The zebrafish larva is an ideal model for kidney research due to the vast amount of offsprings, the rapid development of a simple kidney and a remarkable homology to the mammalian glomerulus. Zebrafish larvae possess a size-selective glomerular filtration barrier at 4 days post fertilization including podocytes with interdigitating foot processes that are connected by a slit membrane. Adriamycin is an anthracycline which is often used in mice and rats to induce a FSGS-like phenotype. In this study, we aimed to induce a similar phenotype to zebrafish larvae by adding adriamycin to the tank water in different concentrations. Surprisingly, zebrafish larvae did not develop glomerular injury and displayed an intact filtration barrier after treatment with adriamycin. This was shown by (immuno-) histology, our filtration assay, in vivo imaging by 2-photon microcopy, RT-(q)PCR as well as transmission electron microscopy. To summarize, adriamycin is unable to induce a podocyte-related damage in zebrafish larvae and therefore major effort must be made to establish FSGS in zebrafish larvae to identify effective drugs by screenings.

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