scholarly journals Massive Proteinuria-Induced Injury of Tubular Epithelial Cells in Nephrotic Syndrome is Not Exacerbated by Furosemide

2018 ◽  
Vol 45 (4) ◽  
pp. 1700-1706 ◽  
Author(s):  
Shujun Wang ◽  
Qingjun Pan ◽  
Chen Xu ◽  
Jun-jia Li ◽  
Hao-Xuan Tang ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Clinical Study ◽  
Epithelial Cells ◽  
Urine Volume ◽  
Human Kidney ◽  
Control Group ◽  
Tubular Epithelial Cells ◽  
Short Term Treatment ◽  
Vacuolar Degeneration

Background/Aims: Massive proteinuria, a significant sign of nephrotic syndrome (NS), has the potential to injure tubular epithelial cells (TECs). Furosemide is widely used for the treatment of edema, a common manifestation of NS. However, whether furosemide treatment affects massive proteinuria-induced TEC injury in patients with NS is unknown. Methods: The effect of furosemide on TEC damage was investigated in vitro. In addition, a clinical study was conducted to study whether the short-term treatment of nephrotic edema with furosemide could exacerbate TEC injury. Results: The proliferation of in vitro human kidney-2 (HK-2) cells exposed to massive urinary protein (8 mg/mL) significantly decreased (P<0.05), while the levels of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase associated lipocalin (NGAL) in the supernatants significantly increased (P<0.05). Importantly, furosemide treatment did not further increase the expression of Kim-1 and NGAL in HK-2 cells upregulated by massive proteinuria. For the clinical study, 26 patients with NS, all prescribed the recommended dosage of prednisone (1 mg/kg/day), were randomly assigned to two groups. One group (n=13) received furosemide (60-120 mg/day, intravenously) for 1 week; the remaining participants (control group) did not receive furosemide or any other diuretics. The results showed that the 24-h urine volume in the furosemide-treated group was slightly, but not significantly, higher than that in the control group (P>0.05). In addition, serum levels of BUN, Scr, Cys C, and urinary Kim-1 and NGAL were not significantly different between the two groups (all P>0.05). Twenty-three patients underwent a renal biopsy. Of these, 22 patients exhibited vacuolar degeneration of the TECs; 8 patients showed brush border membrane shedding of the TECs; and 12 patients showed protein casts. However, there were no significant differences between the two groups (all P>0.05). Conclusion: In summary, massive proteinuria induced the injury of TECs in patients with NS, and furosemide treatment did not aggravate this injury.

scholarly journals BKV and SV40 infection of human kidney tubular epithelial cells in vitro

Virology ◽  
2004 ◽  
Vol 323 (2) ◽  
pp. 182-188 ◽  
Author(s):  
Jonathan Low ◽  
H.David Humes ◽  
Mark Szczypka ◽  
Michael Imperiale
Keyword(s):  
Epithelial Cells ◽  
Human Kidney ◽  
Tubular Epithelial Cells ◽  
Sv40 Infection

scholarly journals A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation

2018 ◽  
Vol 29 (12) ◽  
pp. 2820-2833 ◽  
Author(s):  
Maria B. Monteiro ◽  
Susanne Ramm ◽  
Vidya Chandrasekaran ◽  
Sarah A. Boswell ◽  
Elijah J. Weber ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Human Kidney ◽  
Tubular Epithelial Cell ◽  
Epithelial Cell Proliferation ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

BackgroundThe death of epithelial cells in the proximal tubules is thought to be the primary cause of AKI, but epithelial cells that survive kidney injury have a remarkable ability to proliferate. Because proximal tubular epithelial cells play a predominant role in kidney regeneration after damage, a potential approach to treat AKI is to discover regenerative therapeutics capable of stimulating proliferation of these cells.MethodsWe conducted a high-throughput phenotypic screen using 1902 biologically active compounds to identify new molecules that promote proliferation of primary human proximal tubular epithelial cells in vitro.ResultsThe primary screen identified 129 compounds that stimulated tubular epithelial cell proliferation. A secondary screen against these compounds over a range of four doses confirmed that eight resulted in a significant increase in cell number and incorporation of the modified thymidine analog EdU (indicating actively proliferating cells), compared with control conditions. These eight compounds also stimulated tubular cell proliferation in vitro after damage induced by hypoxia, cadmium chloride, cyclosporin A, or polymyxin B. ID-8, an inhibitor of dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), was the top candidate identified as having a robust proproliferative effect in two-dimensional culture models as well as a microphysiologic, three-dimensional cell culture system. Target engagement and genetic knockdown studies and RNA sequencing confirmed binding of ID-8 to DYRK1A and upregulation of cyclins and other cell cycle regulators, leading to epithelial cell proliferation.ConclusionsWe have identified a potential first-in-class compound that stimulates human kidney tubular epithelial cell proliferation after acute damage in vitro.

Interleukin-1α enhances the biosynthesis of complement C3 and factor B by human kidney proximal tubular epithelial cells in vitro

1996 ◽  
Vol 33 (10) ◽  
pp. 847-854 ◽  
Author(s):  
Jort S.J. Gerritsma ◽  
Arnout F. Gerritsen ◽  
Cees Van Kooten ◽  
Leendert A. Van Es ◽  
Mohamed R. Daha
Keyword(s):  
Epithelial Cells ◽  
Human Kidney ◽  
Complement C3 ◽  
Tubular Epithelial Cells ◽  
Factor B ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Interleukin 1Α

scholarly journals PM2.5 exposure induces renal injury via the activation of the autophagic pathway in rat and HK-2 cell

2020 ◽  
Author(s):  
Xiaoliu Huang ◽  
Jue Li
Keyword(s):  
Epithelial Cells ◽  
Renal Injury ◽  
Fine Particulate Matter ◽  
Human Kidney ◽  
Kidney Damage ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular

Abstract Background Exposure to airborne fine particulate matter (PM2.5) has been declared to be harmful to the human kidney. However, whether activation of the autophagic pathway plays key roles in the nephrotoxicity caused by PM2.5 exposure is still poorly understood. The aim of this study was to explore the mechanism of kidney damage after PM2.5 exposure in vivo and in vitro. Results In the present study, statistically significant alterations in water intake, urine flow rate and mean blood pressure were observed between the PM2.5 group and FA group during the period of PM2.5 exposure. Exposed animals showed severe edema of renal tubular epithelial cells, capillary congestion, reduction of the glomerular urinary space and early pro-fibrotic state. Moreover, significant increases in the levels of early kidney damage markers were observed in the exposed rats and these animals exhibited more apoptosis rate in kidney cells. In addition, PM2.5 exposure resulted in the activation of the autophagic pathway, as evidenced by LC3-I to LC3-II conversion, P62 and beclin-1 activated. All of these effects are in concurrence with the presence of more autophagosomes both in vivo and in vitro after PM2.5 exposure. Conclusions Taken together, our findings indicated that PM2.5-induced renal injury via the activation of the autophagic pathway in renal tubular epithelial cells.

scholarly journals Mitochondria Permeability Transition versus Necroptosis in Oxalate-Induced AKI

2019 ◽  
Vol 30 (10) ◽  
pp. 1857-1869 ◽  
Author(s):  
Shrikant Ramesh Mulay ◽  
Mohsen M. Honarpisheh ◽  
Orestes Foresto-Neto ◽  
Chongxu Shi ◽  
Jyaysi Desai ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Calcium Oxalate ◽  
Mitochondrial Permeability Transition ◽  
Human Kidney ◽  
Permeability Transition ◽  
Calcium Pyrophosphate Dihydrate ◽  
Tubular Epithelial Cells ◽  
Mitochondrial Permeability ◽  
Regulated Necrosis

BackgroundSerum oxalate levels suddenly increase with certain dietary exposures or ethylene glycol poisoning and are a well known cause of AKI. Established contributors to oxalate crystal–induced renal necroinflammation include the NACHT, LRR and PYD domains-containing protein-3 (NLRP3) inflammasome and mixed lineage kinase domain-like (MLKL) protein–dependent tubule necroptosis. These studies examined the role of a novel form of necrosis triggered by altered mitochondrial function.MethodsTo better understand the molecular pathophysiology of oxalate-induced AIK, we conducted in vitro studies in mouse and human kidney cells and in vivo studies in mice, including wild-type mice and knockout mice deficient in peptidylprolyl isomerase F (Ppif) or deficient in both Ppif and Mlkl.ResultsCrystals of calcium oxalate, monosodium urate, or calcium pyrophosphate dihydrate, as well as silica microparticles, triggered cell necrosis involving PPIF–dependent mitochondrial permeability transition. This process involves crystal phagocytosis, lysosomal cathepsin leakage, and increased release of reactive oxygen species. Mice with acute oxalosis displayed calcium oxalate crystals inside distal tubular epithelial cells associated with mitochondrial changes characteristic of mitochondrial permeability transition. Mice lacking Ppif or Mlkl or given an inhibitor of mitochondrial permeability transition displayed attenuated oxalate-induced AKI. Dual genetic deletion of Ppif and Mlkl or pharmaceutical inhibition of necroptosis was partially redundant, implying interlinked roles of these two pathways of regulated necrosis in acute oxalosis. Similarly, inhibition of mitochondrial permeability transition suppressed crystal-induced cell death in primary human tubular epithelial cells. PPIF and phosphorylated MLKL localized to injured tubules in diagnostic human kidney biopsies of oxalosis-related AKI.ConclusionsMitochondrial permeability transition–related regulated necrosis and necroptosis both contribute to oxalate-induced AKI, identifying PPIF as a potential molecular target for renoprotective intervention.

scholarly journals PM2.5 exposure induced renal injury via the activation of the autophagic pathway in the rat and HK-2 cell

2020 ◽  
Author(s):  
Xiaoliu Huang ◽  
Zhitong Zhou ◽  
Xinwen Liu ◽  
Jue Li ◽  
Lijuan Zhang
Keyword(s):  
Epithelial Cells ◽  
Fine Particulate Matter ◽  
Human Kidney ◽  
Kidney Damage ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Function Impairment ◽  
Renal Tubular

Abstract Background: Exposure to airborne fine particulate matter (PM2.5) has been declared to be harmful to human kidney. However, whether activation of the autophagic pathway plays key roles in the nephrotoxicity caused by PM2.5 exposure is still poorly understood. The aim of this study was to explore the mechanism of kidney damage after PM2.5 exposure in vivo and in vitro.Results: In the present study, statistically significant alterations in water intake, urine flow rate and mean blood pressure were observed between the concentrated PM2.5 (PM2.5) group and the filtered air (FA) group. Exposed animals showed severe edema of renal tubular epithelial cells, capillary congestion, reduction of the glomerular urinary space and early pro-fibrotic state. Moreover, significant increases in the levels of early kidney damage markers were observed in the exposed rats and these animals exhibited more apoptosis rate in kidney cells. In addition, PM2.5 exposure activated the autophagic pathway, as evidenced by LC3-I to LC3-II conversion, activation of P62 and beclin-1. All of these effects are in concurrence with the presence of more autophagosomes both in vivo and in vitro after PM2.5 exposure. Conclusions: Taken together, our findings indicated that PM2.5-induced renal function impairment via the activation of the autophagic pathway in renal tubular epithelial cells.

scholarly journals Urine-Derived Epithelial Cells as Models for Genetic Kidney Diseases

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1413
Author(s):  
Tjessa Bondue ◽  
Fanny O. Arcolino ◽  
Koenraad R. P. Veys ◽  
Oyindamola C. Adebayo ◽  
Elena Levtchenko ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Kidney Diseases ◽  
Cell Types ◽  
Cell Models ◽  
Tubular Epithelial Cells ◽  
Disease Mechanisms ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Disease Cell

Epithelial cells exfoliated in human urine can include cells anywhere from the urinary tract and kidneys; however, podocytes and proximal tubular epithelial cells (PTECs) are by far the most relevant cell types for the study of genetic kidney diseases. When maintained in vitro, they have been proven extremely valuable for discovering disease mechanisms and for the development of new therapies. Furthermore, cultured patient cells can individually represent their human sources and their specific variants for personalized medicine studies, which are recently gaining much interest. In this review, we summarize the methodology for establishing human podocyte and PTEC cell lines from urine and highlight their importance as kidney disease cell models. We explore the well-established and recent techniques of cell isolation, quantification, immortalization and characterization, and we describe their current and future applications.

Sign in / Sign up

Export Citation Format

Share Document