Renal cell culture models: Contribution to the understanding of nephrotoxic mechanisms

Jennings, Paul; Koppelstätter, Christian; Lechner, Judith; Pfaller, Walter

doi:10.1007/978-0-387-84843-3_10

Cited by 6 publications

(2 citation statements)

References 211 publications

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“…In the kidney alone, more than 12 morphologically distinct types of epithelial cells have been described (1). The proximal tubule is the main site of reabsorption in the nephron and is considered a "leaky" epithelium due to the expression of pore-forming claudins 2 and 10 in the tight junctions (2).…”

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confidence: 99%

Delineation of the Key Aspects in the Regulation of Epithelial Monolayer Formation

Aschauer

Grüber

Pfaller

et al. 2013

Molecular and Cellular Biology

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The formation, maintenance, and repair of epithelial barriers are of critical importance for whole-body homeostasis. However, the molecular events involved in epithelial tissue maturation are not fully established. To this end, we investigated the molecular processes involved in renal epithelial proximal-tubule monolayer maturation utilizing transcriptomic, metabolomic, and functional parameters. We uncovered profound dynamic alterations in transcriptional regulation, energy metabolism, and nutrient utilization over the maturation process. Proliferating cells exhibited high glycolytic rates and high transcript levels for fatty acid synthesis genes (FASN), whereas matured cells had low glycolytic rates, increased oxidative capacity, and preferentially expressed genes for beta oxidation. There were dynamic alterations in the expression and localization of several adherens (CDH1, -4, and -16) and tight junction (TJP3 and CLDN2 and -10) proteins. Genes involved in differentiated proximal-tubule function, cilium biogenesis (BBS1), and transport (ATP1A1 and ATP1B1) exhibited increased expression during epithelial maturation. Using TransAM transcription factor activity assays, we could demonstrate that p53 and FOXO1 were highly active in matured cells, whereas HIF1A and c-MYC were highly active in proliferating cells. The data presented here will be invaluable in the further delineation of the complex dynamic cellular processes involved in epithelial cell regulation.

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confidence: 99%

Delineation of the Key Aspects in the Regulation of Epithelial Monolayer Formation

Aschauer

Grüber

Pfaller

et al. 2013

Molecular and Cellular Biology

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“…It was found that renal epithelial cells of the proximal nephron are a target for nephrotoxic compounds due to a large number of transport systems and the presence of xenobiotic metabolizing enzymes such as cytochrome P-450, glucuronyl transferase, sulfotransferases, glutathione S-transferases and others [53]. The histopathological analysis of kidneys from mice treated with extract of H. kuetzingii showed alteration of the integrity of the proximal and distal convoluted tubules, infiltration of leukocytes and congestion of the blood vessels.…”

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confidence: 99%

In vitro and in vivo toxicity evaluation of the freshwater cyanobacterium Heteroleiblenia kuetzingii

et al. 2013

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Cyanobacteria are prokaryotic organisms characterized by their ability to produce secondary metabolites with different biological activities. The aim of this work was to evaluate the in vitro and in vivo toxicity of the cosmopolitan freshwater cyanobacterium H. kuetzingii. An extract from H. kuetzingii and cyanobacterial growth media were assessed for presence of intracellular and extracellular toxins by in vitro tests using primary cell cultures from mouse kidney and fibroblasts, cell lines A549 and 3T3, a fish cell line RTgill-W1 as well as by a traditional in vivo mouse bioassay. The presence of toxicity was compared with the ELISA and HPLC data for corresponding cyanotoxins. In vitro tests showed pronounced cytotoxicity of the cyanobacterium extract and growth medium in which H. kuetzingii released potential extracellular toxic compounds as the mammalian cells were significantly more sensitive to exposure compared to the fish cells. Histopathological analyses of the liver and kidneys of treated mice showed pathological changes such as leukocyte infiltration and necrosis, changes in the proximal and distal convoluted tubules, lack of differentiation of Bowman's space, enlarged Bowman's capsules and massive hemorrhages. ELISA and HPLC analyses confirmed the presence of saxitoxins and microcystins at low concentrations. In addition, the histological analyses suggest that H. kuetzingii produces other, yet unknown toxic metabolites. Monitoring efforts are therefore required to evaluate the potential hazard for the freshwater aquatic systems and possible public health implications associated with this cyanobacterium.

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In VitrotoIn VivoRelationships with Respect to Kidney Safety Biomarkers

Jennings

2016

Drug Discovery Toxicology

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Renal cell culture models: Contribution to the understanding of nephrotoxic mechanisms

Cited by 6 publications

References 211 publications

Delineation of the Key Aspects in the Regulation of Epithelial Monolayer Formation

Delineation of the Key Aspects in the Regulation of Epithelial Monolayer Formation

In vitro and in vivo toxicity evaluation of the freshwater cyanobacterium Heteroleiblenia kuetzingii

In VitrotoIn VivoRelationships with Respect to Kidney Safety Biomarkers

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