scholarly journals The glomerular endothelial cell coat is essential for glomerular filtration

2011 ◽  
Vol 79 (12) ◽  
pp. 1322-1330 ◽  
Author(s):  
Vincent Fridén ◽  
Eystein Oveland ◽  
Olav Tenstad ◽  
Kerstin Ebefors ◽  
Jenny Nyström ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Glomerular Filtration ◽  
Glomerular Endothelial Cell ◽  
Cell Coat

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 Loss of filtration function in diabetic glomeruli is associated with ultrastructural changes in glomerular endothelial cell fenestrations

2020 ◽  
Author(s):  
Natalie Finch ◽  
Sarah Fawaz ◽  
Chris Neal ◽  
Matthew Butler ◽  
Vivian Lee ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Endothelial Cell ◽  
Glomerular Filtration ◽  
Critical Role ◽  
Ultrastructural Changes ◽  
Glomerular Endothelial Cell ◽  
Functional Changes ◽  
Glomerular Ultrafiltration

Background: The study of glomerular endothelial cell (GEnC) fenestrations including key regulatory factors is neglected despite their loss in diabetic nephropathy, a disease associated with decreased filtration function, being previously described. Methods: We comprehensively characterised GEnC fenestral and renal filtration functional changes including measurement of glomerular ultrafiltration coefficient and glomerular filtration rate (GFR) in diabetic mice and humans. We further evaluated Eps homology domain protein-3 (Ehd3) as a potential regulator of GEnC fenestrations. Results: This study identified loss of GEnC fenestration density which was associated with decreased renal filtration function in diabetic nephropathy. We also identified increased GEnC fenestration width, an ultrastructural change that may develop to maintain filtration surface area. GEnC fenestration width was negatively associated with renal filtration function considered a result of development of diaphragms in widening fenestrations providing resistance to filtration. The increased presence of diaphragmed fenestrations in diabetes was supported by increased PLVAP1 expression. We identified decreased glomerular Ehd3 expression in diabetes and demonstrated its association with GEnC fenestration measurements suggesting its role in regulating fenestrations. We further demonstrated reduced fenestration formation in vitro in an Ehd3 knockdown cell line. Ehd3 was positively associated with filtration function suggesting loss of glomerular Ehd3 expression in disease may contribute to declining glomerular filtration function through aberrant GEnC fenestration regulation. Conclusions: This is the first study to demonstrate the critical role of GEnC fenestrations in renal filtration function and identify a key regulator, Ehd3, that may serve as a therapeutic target to retore filtration function in disease.

scholarly journals FC 029PODOCYTE AND GLOMERULAR ENDOTHELIAL CELL DERIVED MICRORNAS REGULATE PODOCYTE NEPHRONECTIN IN MEMBRANOUS GLOMERULONEPHRITIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Janina Müller-Deile ◽  
Nina Sopel ◽  
Alexandra Ohs ◽  
Ahmed Kotb ◽  
Groener Marwin ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Glomerular Filtration ◽  
Structural Changes ◽  
Membranous Glomerulonephritis ◽  
Glomerular Endothelial Cell ◽  
Glomerular Filtration Barrier ◽  
Filter Function ◽  
Filtration Barrier ◽  
Phospholipase A2 Receptor ◽  
Complex Deposition

Abstract Background and Aims Autoantibodies binding to podocyte antigens cause idiopathic membranous glomerulonephritis (iMGN). However, it remains elusive how autoantibodies reach the subepithelial space because the glomerular filtration barrier is normally size selective and impermeable for antibodies. Method Kidney biopsies from patients with MGN, cell culture, zebrafish and mice models were used to investigate the role of nephronectin (NPNT) regulating microRNAs (miRs) for the glomerular filtration barrier. Results We found that endothelial cell-derived miR-192-5p and podocyte-derived miR-378a-3p are upregulated in patients with anti-phospholipase A2 receptor antibody positive (PLA2R-ab+) iMGN and regulate glomerular NPNT expression (Fig. 1). Overexpression of miR-378a-3p and miR-192-5p as well as morpholino mediated npnt knockdown in zebrafish induced edema, proteinuria, loss of podocyte markers and podocyte effacement. The most prominent phenotype however were structural changes of the glomerular basement membrane (GBM) with increased lucidity, slicing and lamellation especially of the lamina rara interna (Fig. 2, Fig. 3). The phenotype was comparable to ultrastructural findings seen in iMGN. IgG sized nanoparticles accumulated in lucidity areas of the lamina rara interna and lamina densa of the GBM in npnt knockdown zebrafish models. Loss of slit diaphragm proteins and severe structural impairment of the GBM were further confirmed in podocyte specific Npnt knockout mice (Fig. 4). Conclusion Podocyte NPNT is important for proper glomerular filter function and GBM structure and is regulated by podocyte and glomerular endothelial cell derived miRs. We hypothesize that loss of NPNT in the GBM is part of the pathophysiology of iMGN and enables subepithelial immune complex deposition in iMGN.

CD8+iTregs attenuate glomerular endothelial cell injury in lupus-prone mice through blocking the activation of p38 MAPK and NF-κB

2018 ◽  
Vol 103 ◽  
pp. 133-143 ◽  
Author(s):  
Ya Liu ◽  
Weijuan Deng ◽  
Qiaoyun Meng ◽  
Xiaonan Qiu ◽  
Dong Sun ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
P38 Mapk ◽  
Cell Injury ◽  
Glomerular Endothelial Cell ◽  
Endothelial Cell Injury
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