scholarly journals Cosmc-dependent mucin-type O-linked glycosylation is essential for podocyte function

2020 ◽  
Vol 318 (2) ◽  
pp. F518-F530
Author(s):  
Brian R. Stotter ◽  
Brianna E. Talbot ◽  
Diane E. Capen ◽  
Nadine Artelt ◽  
Junwei Zeng ◽  
...  
Keyword(s):  
Renal Failure ◽  
Glomerular Sclerosis ◽  
Tn Antigen ◽  
Foot Process Effacement ◽  
Hemizygous Male ◽  
Podocyte Loss ◽  
A Cell ◽  
Foot Process ◽  
Matrix Organization ◽  
The Stability

Mucin-type O-linked glycosylation, a posttranslational modification affecting the stability and biophysical characteristics of proteins, requires C1GalT1 (T synthase) and its obligate, X-linked chaperone Cosmc. Hypomorphic C1GalT1 mutations cause renal failure via not yet established mechanisms. We hypothesize that impaired Cosmc-dependent O-glycosylation in podocytes is sufficient to cause disease. Podocyte-specific Cosmc knockout mice were generated and phenotyped to test this hypothesis. Female heterozygous mice displaying mosaic inactivation of Cosmc in podocytes due to random X-linked inactivation were also examined. Mice with podocyte-specific Cosmc deletion develop profound albuminuria, foot process effacement, glomerular sclerosis, progressive renal failure, and impaired survival. Glomerular transcriptome analysis reveals early changes in cell adhesion, extracellular matrix organization, and chemokine-mediated signaling pathways, coupled with podocyte loss. Expression of the O-glycoprotein podoplanin was lost, while Tn antigen, representing immature O-glycans, was most abundantly found on podocalyxin. In contrast to hemizygous male and homozygous female animals, heterozygous female mosaic animals developed only mild albuminuria, focal foot process effacement, and nonprogressive kidney disease. Ultrastructurally, Cosmc-deficient podocytes formed Tn antigen-positive foot processes interdigitating with those of normal podocytes but not with other Cosmc-deficient cells. This suggests a cell nonautonomous mechanism for mucin-type O-glycoproteins in maintaining podocyte function. In summary, our findings demonstrated an essential and likely cell nonautonomous role for mucin-type O-glycosylation for podocyte function.

scholarly journals Dosage-dependent role of Rac1 in podocyte injury

2016 ◽  
Vol 310 (8) ◽  
pp. F777-F784 ◽  
Author(s):  
Xiaoyang Wan ◽  
Mi-Sun Lee ◽  
Weibin Zhou
Keyword(s):  
Kidney Injury ◽  
Small Gtpase ◽  
Glomerular Sclerosis ◽  
Transgenic Zebrafish ◽  
Dependent Manner ◽  
Podocyte Injury ◽  
Filtration Barrier ◽  
Foot Process Effacement ◽  
Rac1 Activity ◽  
Foot Process

Activation of small GTPase Rac1 in podocytes is associated with rodent models of kidney injury and familial nephrotic syndrome. Induced Rac1 activation in podocytes in transgenic mice results in rapid transient proteinuria and foot process effacement, but not glomerular sclerosis. Thus it remains an open question whether abnormal activation of Rac1 in podocytes is sufficient to cause permanent podocyte damage. Using a number of transgenic zebrafish models, we showed that moderate elevation of Rac1 activity in podocytes did not impair the glomerular filtration barrier but aggravated metronidazole-induced podocyte injury, while inhibition of Rac1 activity ameliorated metronidazole-induced podocyte injury. Furthermore, a further increase in Rac1 activity in podocytes was sufficient to cause proteinuria and foot process effacement, which resulted in edema and lethality in juvenile zebrafish. We also found that activation of Rac1 in podocytes significantly downregulated the expression of nephrin and podocin, suggesting an adverse effect of Rac1 on slit diaphragm protein expression. Taken together, our data have demonstrated a causal link between excessive Rac1 activity and podocyte injury in a dosage-dependent manner, and transgenic zebrafish of variable Rac1 activities in podocytes may serve as useful animal models for the study of Rac1-related podocytopathy.

scholarly journals Effects of Perfusion Pressures on Podocyte Loss in the Isolated Perfused Mouse Kidney.

2021 ◽  
Vol 55 (S4) ◽  
pp. 1-12
Keyword(s):  
Ex Vivo ◽  
Early Time ◽  
Filtration Flow ◽  
Glomerular Diseases ◽  
Aged Mice ◽  
Foot Process Effacement ◽  
Podocyte Detachment ◽  
Podocyte Loss ◽  
Foot Process ◽  
Young Mice

BACKGROUND/AIMS: Podocytes are lost in most glomerular diseases, leading to glomerulosclerosis and progressive kidney disease. It is generally assumed, that podocytes are exposed to the filtration flow and thus to significant shear forces driving their detachment from the glomerular basement membrane (GBM). In this context, foot process effacement has been proposed as potential adaptive response to increase adhesion of podocytes to the GBM. METHODS: We have tested these hypotheses using optical clearing and high-resolution 3-dimensional morphometric analysis in the isolated perfused murine kidney. We investigated the dynamics of podocyte detachment at different perfusion pressures (50, 300 and more than 450 mmHg) in healthy young or old mice (20 vs. 71 weeks of age), or mice injected with anti-GBM serum to induce global foot process effacement. RESULTS: Results show that healthy podocytes in young mice are tightly attached onto the GBM and even supramaximal pressures did not cause significant detachment. Compared to young mice, in aged mice and mice with anti-GBM nephritis and foot process effacement, gradual progressive loss of podocytes had occurred already before perfusion. High perfusion pressures resulted in a relatively minor additional loss of podocytes in aged mice. In mice with anti-GBM nephritis significant additional podocyte loss occurred at this early time point when increasing perfusion pressures to 300 mmHg or higher. CONCLUSION: This work provides the first experimental evidence that podocytes are extraordinarily resistant to acutely increased perfusion pressures in an ex vivo isolated kidney perfusion model. Only in glomerular disease, significant numbers of injured podocytes detached following acute increases in perfusion pressure.

Using FRET to Measure the Time it Takes for a Cell to Destroy a Virus

2019 ◽  
Author(s):  
Candace E. Benjamin ◽  
Zhuo Chen ◽  
Olivia Brohlin ◽  
Hamilton Lee ◽  
Stefanie Boyd ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Rhodamine B ◽  
Virus Like Particle ◽  
A Cell ◽  
Viral Nanoparticles ◽  
The Stability ◽  
Open Question ◽  
Viral Surface ◽  
Fret Pair

<div><div><div><p>The emergence of viral nanotechnology over the preceding two decades has created a number of intellectually captivating possible translational applications; however, the in vitro fate of the viral nanoparticles in cells remains an open question. Herein, we investigate the stability and lifetime of virus-like particle (VLP) Qβ - a representative and popular VLP for several applications - following cellular uptake. By exploiting the available functional handles on the viral surface, we have orthogonally installed the known FRET pair, FITC and Rhodamine B, to gain insight of the particle’s behavior in vitro. Based on these data, we believe VLPs undergo aggregation in addition to the anticipated proteolysis within a few hours of cellular uptake.</p></div></div></div>

scholarly journals Podocyte Foot Process Effacement in Postreperfusion Allograft Biopsies

2014 ◽  
Vol 97 (7) ◽  
pp. e38-e39
Author(s):  
George W. Burke ◽  
Jei-Wen Chang ◽  
Victoriano Pardo ◽  
Junichiro Sageshima ◽  
Linda Chen ◽  
...  
Keyword(s):  
Foot Process Effacement ◽  
Foot Process

scholarly journals ГІСТОЛОГІЧНА ДІАГНОСТИКА ХРОНІЧНОЇ НИРКОВОЇ НЕДОСТАТНОСТІ В КОТІВ

2016 ◽  
Vol 18 (3(70)) ◽  
pp. 17-21
Author(s):  
B.V. Borysevich ◽  
V. Sviridenko ◽  
V.V. Hunich
Keyword(s):  
Renal Failure ◽  
Kidney Failure ◽  
Clinical Signs ◽  
Chronic Kidney Failure ◽  
Glomerular Sclerosis ◽  
Kidney Cells ◽  
Paraffin Sections ◽  
Blood Capillaries ◽  
Histological Studies ◽  
Laboratory Results

The objective of the study is to set the criteria of histological diagnosis of chronic renal insufficiency in cats. Lifetime diagnosis of chronic renal failure in a complex was set in complex, basing on anamnesis, clinical signs and laboratory results of blood and urine. For histological studies 29 cats corpses of different breeds and ages were used, who died from chronic kidney failure. Paraffin sections of 7 – 10 mm thickness from the different segments of kidney were stained with Carazzi's hematoxylin and eosin.It was established that during the histological studies in the kidney of cats who died from chronic kidney failure the microscopic changes diversity is characteristic. A characteristic feature of chronic kidney failure cats is complex of changes, which includes: 1) expand and overflow of blood capillaries of the glomeruli; 2) sludge–phenomenon in the capillaries of the glomerulus; 3) lack of blood in the capillaries of the glomerulus; 4) an increased amount of leachate in the cavity of Boumen–Shumlyanskiy capsule; 5) thickening (in some casescrescent–like) of parietal layer of Boumen–Shumlyanskiy capsule due to the hypertrophy and hyperplasia of its cells in the part of kidney cells; 6) glomerular sclerosis of the renal corpuscles and total necrosis of the renal corpuscles; 7) microcysts formation, mainly in the cortex. Other microscopic changes in different animals vary. 

scholarly journals armadillo, bazooka, and stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila.

1996 ◽  
Vol 134 (1) ◽  
pp. 149-163 ◽  
Author(s):  
H A Müller ◽  
E Wieschaus
Keyword(s):  
Plasma Membranes ◽  
Basolateral Membrane ◽  
Cell Sheet ◽  
Cell Monolayer ◽  
Test System ◽  
Sem Analysis ◽  
Drosophila Embryo ◽  
Early Stages ◽  
A Cell ◽  
The Stability

Cellularization of the Drosophila embryo results in the formation of a cell monolayer with many characteristics of a polarized epithelium. We have used antibodies specific to cellular junctions and nascent plasma membranes to study the formation of the zonula adherens (ZA) in relation to the establishment of basolateral membrane polarity. The same approach was then used as a test system to identify X-linked zygotically active genes required for ZA formation. We show that ZA formation begins during cellularization and that the basolateral membrane domain is established at mid-gastrulation. By creating deficiencies for defined regions of the X chromosome, we have identified genes that are required for the formation of the ZA and the generation of basolateral membrane polarity. We show that embryos mutant for both stardust (sdt) and bazooka (baz) fail to form a ZA. In addition to the failure to establish the ZA, the formation of the monolayered epithelium is disrupted after cellularization, resulting in formation of a multilayered cell sheet by mid-gastrulation. SEM analysis of mutant embryos revealed a conversion of cells exhibiting epithelial characteristics into cells exhibiting mesenchymal characteristics. To investigate how mutations that affect an integral component of the ZA itself influence ZA formation, we examined embryos with reduced maternal and zygotic supply of wild-type Arm protein. These embryos, like embryos mutant for both sdt and baz, exhibit an early disruption of ZA formation. These results suggest that early stages in the assembly of the ZA are critical for the stability of the polarized blastoderm epithelium.

Epithelial Foot-process Effacement in Patients with Proteinuria

1979 ◽  
Vol 72 (4) ◽  
pp. 529-532 ◽  
Author(s):  
William M. Murphy ◽  
Frank L. Moretta ◽  
Alina F. Jukkola
Keyword(s):  
Foot Process Effacement ◽  
Foot Process
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