scholarly journals Histomorphology and Immunohistochemistry of a Congenital Nephromegaly Demonstrate Concurrent Features of Heritable and Acquired Cystic Nephropathies in a Girgentana Goat (Capra falconeri)

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Christian Mayer ◽  
Steffen Ormanns ◽  
Monir Majzoub-Altweck
Keyword(s):  
Kidney Diseases ◽  
Renal Tissue ◽  
Renal Parenchyma ◽  
Biliary Duct ◽  
Differentiation Markers ◽  
Mesenchymal Transition ◽  
Tissue Sections ◽  
Renal Tubular Epithelium ◽  
First Case ◽  
Renal Tubular

Polycystic kidney diseases (PKD) represent frequent congenital and adult nephropathies in humans and domestic animals. This report illustrates an uncommon state of congenital PKD in a girgentana goat (Capra falconeri). A stillborn female goat kid was submitted for postmortem examination and underwent macroscopic and microscopic examination. The kidneys showed a bilateral nephromegaly and a perpendicular polycystic altered texture of the renal parenchyma. Renal tissue sections were comprehensively investigated by histopathology (overview and special stains), immunohistochemistry (CD10, CD117, pan-cytokeratin, cytokeratin 7, E-cadherin, Pax2, Pax8, and vimentin), and electron microscopy (SEM, TEM). Histopathology of renal tissue sections revealed polycystic alterations of the renal parenchyma as well as conspicuous polypoid proliferates/projections of the renal tubular epithelium, which showed clear cell characteristics. Furthermore, epithelial projections were indicative for epithelio-mesenchymal-transition, cellular depolarization, and strong expression of differentiation markers Pax2, Pax8, and CD10. Ultrastructural morphology of the projections was characterized by numerous diffusely distributed, demarked round cytoplasmic structures and several apico-lateral differentiations. Additionally, hepatic malformations comprising biliary duct proliferation with saccular dilation and bridging fibrosis were observed. Notably, this report describes the first case of a congenital cystic nephropathy with overlapping features of heritable and acquired nephropathies in any species. Epithelio-mesenchymal-transition and altered cadherin expression seem to be crucial components of a suspected pathomechanism during cystogenesis.

scholarly journals Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2

2020 ◽  
Vol 31 (8) ◽  
pp. 1683-1687 ◽  
Author(s):  
Evan A. Farkash ◽  
Allecia M. Wilson ◽  
Jeffrey M. Jentzen
Keyword(s):  
Renal Failure ◽  
Light Microscopy ◽  
Virus Assembly ◽  
Light And Electron Microscopy ◽  
Membrane Vesicles ◽  
Renal Tissue ◽  
Double Membrane ◽  
Renal Tubular Epithelium ◽  
Renal Tubular ◽  
Renal Infection

BackgroundA significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%–7% progressing to ARF, a marker of poor prognosis. The cause of the renal failure in COVID-19 is unknown, but one hypothesized mechanism is direct renal infection by the causative virus, SARS-CoV-2.MethodsWe performed an autopsy on a single patient who died of COVID-19 after open repair of an aortic dissection, complicated by hypoxic respiratory failure and oliguric renal failure. We used light and electron microscopy to examine renal tissue for evidence of SARS-CoV-2 within renal cells.ResultsLight microscopy of proximal tubules showed geographic isometric vacuolization, corresponding to a focus of tubules with abundant intracellular viral arrays. Individual viruses averaged 76 µm in diameter and had an envelope studded with crown-like, electron-dense spikes. Vacuoles contained double-membrane vesicles suggestive of partially assembled virus.ConclusionsThe presence of viral particles in the renal tubular epithelium that were morphologically identical to SARS-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-CoV-2. This finding offers confirmatory evidence that direct renal infection occurs in the setting of AKI in COVID-19. However, the frequency and clinical significance of direct infection in COVID-19 is unclear. Tubular isometric vacuolization observed with light microscopy, which correlates with double-membrane vesicles containing vacuoles observed with electronic microscopy, may be a useful histologic marker for active SARS-CoV-2 infection in kidney biopsy or autopsy specimens.

Abstract 132: Hypoxia-inducible Factor Prolyl-hydroxylase-2 Mediates Transforming Growth Factor Beta 1-induced Epithelial-mesenchymal Transition In Renal Tubular Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Weiqing Han ◽  
Jun-Pin Hu ◽  
Pin-Lan Li ◽  
Ningjun Li
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Hypoxia Inducible Factor ◽  
Mesenchymal Transition ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Transforming growth factor beta 1 (TGFβ1)-induced epithelial-mesenchymal transition (EMT) in kidney epithelial cells plays a key role in renal tubulointerstitial fibrosis in chronic kidney diseases. As hypoxia-inducible factor (HIF)-1α is found to mediate TGFβ1 signaling pathway, we tested the hypothesis that HIF-1α and its upstream regulator prolyl hydroxylase domain-containing proteins (PHDs) are involved in TGFβ1-induced EMT in renal tubular cells. Our results showed that TGFβ1 treatment for 48 h stimulated EMT in cultured renal tubular cells as indicated by the decrease in epithelial marker P-cadherin from 1.0 ± 0.02 to 0.40 ± 0.05 ( P < 0.05), and the increase in mesenchymal markers α-smooth muscle actin (2.14 ± 0.32 fold, P < 0.05) and fibroblast-specific protein (2.0 ± 0.17 fold, P < 0.05) as shown in Western blot assay. Meanwhile, TGFβ1 time-dependently increased HIF-1α, which reached its maximum value (2.36 ± 0.2 fold, P < 0.05) at 24 h, and that HIF-1α siRNA significantly inhibited TGFβ1-induced EMT, suggesting that HIF-1α mediated TGFβ1 induced-EMT. Real-time PCR showed that PHD1 and PHD2, rather than PHD3, could be detected, with PHD2 as the predominant form of PHDs (PHD1 : PHD2 = 0.21:1.0). Importantly, TGFβ1 time-dependently decreased PHD2 mRNA and protein level, which reached their maximum value from 1.0 ± 0.15 to 0.45 ± 0.08 ( P < 0.05) for mRNA at 16 h and from 1.0 ± 0.08 to 0.26 ± 0.08 ( P < 0.05) for protein at 24 h, respectively. In contrast, TGFβ1 had no effect on PHD1 mRNA and protein levels. Furthermore, over-expression of PHD2 transgene almost fully prevented TGFβ1-induced HIF-1α accumulation and EMT marker changes, indicating that PHD2 is involved in TGFβ1-induced EMT. Finally, Smad2 inhibitor SB431542 prevented TGFβ1-induced PHD2 decrease, suggesting that Smad2 may mediate TGFβ1-induced EMT through PHD2/HIF-1α. It is concluded that TGFβ1 decreased PHD2 expression via a Smad2-dependent signaling pathway, thereby leading to HIF-1α accumulation and EMT in renal tubular cells. The present study suggests that PHD2/HIF-1α is a novel signaling pathway mediating the fibrogenic effect of TGFβ1 and that manipulating PHD2/HIF-1α pathway may be used as a therapeutic strategy in chronic kidney diseases. (support: NIH grant HL89563 and HL106042)

scholarly journals Diverse Cell Populations Involved in Regeneration of Renal Tubular Epithelium following Acute Kidney Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Akito Maeshima ◽  
Shunsuke Takahashi ◽  
Masao Nakasatomi ◽  
Yoshihisa Nojima
Keyword(s):  
Stem Cell ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Cell Populations ◽  
Renal Tubules ◽  
Stem Cell Markers ◽  
Tubular Epithelium ◽  
Tubular Cells ◽  
Renal Tubular Epithelium ◽  
Renal Tubular

Renal tubular epithelium has the capacity to regenerate, repair, and reepithelialize in response to a variety of insults. Previous studies with several kidney injury models demonstrated that various growth factors, transcription factors, and extracellular matrices are involved in this process. Surviving tubular cells actively proliferate, migrate, and differentiate in the kidney regeneration process after injury, and some cells express putative stem cell markers or possess stem cell properties. Using fate mapping techniques, bone marrow-derived cells and endothelial progenitor cells have been shown to transdifferentiate into tubular components in vivo or ex vivo. Similarly, it has been demonstrated that, during tubular cell regeneration, several inflammatory cell populations migrate, assemble around tubular cells, and interact with tubular cells during the repair of tubular epithelium. In this review, we describe recent advances in understanding the regeneration mechanisms of renal tubules, particularly the characteristics of various cell populations contributing to tubular regeneration, and highlight the targets for the development of regenerative medicine for treating kidney diseases in humans.

scholarly journals Qualitative analysis of the nephrotoxicity of gold nanoparticles in case of enteral administration

2017 ◽  
Vol 8 (4) ◽  
pp. 32-38
Author(s):  
Veronika A. Lipatova ◽  
Veronika M. Botchey ◽  
Lyudmila A. Knyazeva
Keyword(s):  
Gold Nanoparticles ◽  
Cell Damage ◽  
Single Cells ◽  
Renal Parenchyma ◽  
Ultrastructural Changes ◽  
Colloidal Solutions ◽  
Renal Tubular Epithelium ◽  
Renal Tubular ◽  
A Minor ◽  
Individual Profiles

The experiments on animals show the different effects of gold nanoparticles. Gold particles of various sizes may have a variety of toxic effects on the tissues, and more damage is often produced by small nanoparticles. In this work histological and ultrastructural changes of renal parenchyma caused by enteric administration of gold nanoparticles of small sizes (2 nm) were studied used different concentrations of colloidal solutions of gold nanoparticles: 10 µg/ml; 50 μg/ml; 100 µg/ml in drinking water within 7, 14 and 28 days. There were 9 groups of animals (non-linear mice weighing 20-25 g) on different dates of the experiment, as well as 3 control groups of mice, respectively, each term of experiment. Histological and ultrastructural changes were detected in the material of all groups of experimental animals compared with control. In general all small focal alterations relate to a small number of vessels, individual profiles of tubules and single cells. Light microscopy analysis of the overall picture of integrity of renal parenchyma showed that the most pronounced changes are observed in the cortex of the organ. Medulla is less affected. It identifies, first of all, microvascular disorders, then the renal tubular epithelium changes and finally, a minor involvement of interstitial elements in the response. Tubules of nephrons compared with the renal corpuscles undergo more changes at all dose levels of exposure and in all periods under study. Signs of dystrophy and necrobiosis often relate to the cell cytoplasm and less of their nuclei. Evidence of microvessel disorders detected in the renal cortex is not dependent on the dose of administered nanoparticles already in the early stages of the experiment. Histological findings as a whole are confirmed by the presence of ultrastructure alterations, that points to the primacy of cell damage.

CO2 equilibria in renal tissue

1980 ◽  
Vol 239 (4) ◽  
pp. F307-F318 ◽  
Author(s):  
Gerhard Malnic
Keyword(s):  
Carbonic Acid ◽  
Water Layer ◽  
Renal Tissue ◽  
Buffer System ◽  
Renal Tubules ◽  
Tubular Epithelium ◽  
Renal Tubular Epithelium ◽  
Arterial Blood ◽  
Disequilibrium Ph ◽  
Renal Tubular

Disequilibrium situations within the bicarbonate/CO2 buffer system have been observed in the kidney. On the one hand, a Pco2 difference between final urine and arterial blood has been detected. On the other, a disequilibrium pH was found in cortical renal tubules and attributed to either increased carbonic acid concentrations or to Pco2 levels above those of arterial blood. Recent methodological developments have yielded better insight into these disequilibrium situations. They include, besides the use of pH microelectrodes, the introduction of microcalorimetric total CO2 determinations and Pco2 microelectrodes. There is agreement concerning the finding of a Pco2 10–40 mmHg above that in arterial blood in renal cortical tubules; however, stellate vessel Pco2 equal to tubular Pco2 was found by only one group of investigators. According to their view, diffusion equilibrium exists between all cortical structures, a finding disputed by others using a similar methodology. CO2 permeability of tubular epithelium is also still controversial, with values ranging from one-half (microcalorimetric method) to one-twentieth (pH-equilibration method) of an equivalent water layer having been reported. Two positions emerge on the basis of recent experimental results: the existence of very high permeability to CO2 and consequent diffusion equilibrium in renal cortex, and the occurrence of CO2 diffusion limitation leading to the establishment of finite Pco2 gradients across renal tubular epithelium. disequilibrium pH; CO2 permeability; tubular Pco2; CO22 fluxes; carbonic anhydrase

Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats

2000 ◽  
Vol 278 (1) ◽  
pp. F110-F121 ◽  
Author(s):  
Hirokazu Okada ◽  
Kenshi Moriwaki ◽  
Raghuram Kalluri ◽  
Tsuneo Takenaka ◽  
Hiroe Imai ◽  
...  
Keyword(s):  
Target Genes ◽  
Renal Plasma Flow ◽  
Mrna Level ◽  
Antisense Oligodeoxynucleotide ◽  
Tubular Epithelium ◽  
Rt Pcr ◽  
Goodpasture Syndrome ◽  
Renal Tubular Epithelium ◽  
Protein Excretion ◽  
Renal Tubular

In this study, we have shown that intravenously administered antisense oligodeoxynucleotide (ODN) was demonstrated to be taken up by tubular epithelium, after which it blocked mRNA expression of target genes in normal and nephritic rats. Therefore, we injected osteopontin (OPN) antisense ODN to Goodpasture syndrome (GPS) rats every second day between days 27 and 35, the time when renal OPN expression increased and interstitial monocyte infiltration was aggravated. In parallel to blockade of tubular OPN expression, this treatment significantly attenuated monocyte infiltration and preserved renal plasma flow in GPS rats at day 37, compared with sense ODN-treated and untreated GPS rats. No significant changes were observed in OPN mRNA level by RT-PCR and histopathology of the glomeruli after ODN treatment, which was compatible with an absence of differences in the urinary protein excretion rate. In conclusion, OPN expressed by tubular epithelium played a pivotal role in mediating peritubular monocyte infiltration consequent to glomerular disease.

scholarly journals RNA-seq Characterization of Melanoma Phenotype Switch in 3D Collagen after p38 MAPK Inhibitor Treatment

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 449
Author(s):  
Vladimír Čermák ◽  
Aneta Škarková ◽  
Ladislav Merta ◽  
Veronika Kolomazníková ◽  
Veronika Palušová ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Rna Seq ◽  
Differentiation Markers ◽  
Illumina Hiseq ◽  
Invasive Phenotype ◽  
Mesenchymal Transition ◽  
Phenotype Switch ◽  
3D Collagen ◽  
Phenotype Plasticity

Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid–mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis.

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