The Impact of the Nephrotoxin Ochratoxin A on Human Renal Cells Studied by a Novel Co-Culture Model Is Influenced by the Presence of Fibroblasts
Autor: | Michael Kopf, Gerald Schwerdt, Michael Gekle |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Programmed cell death
Cell type Epithelial-Mesenchymal Transition Health Toxicology and Mutagenesis Cell lcsh:Medicine Apoptosis Cell Communication Mitochondrion Toxicology Article Extracellular matrix Kidney Tubules Proximal 03 medical and health sciences Necrosis energy metabolism medicine Humans apoptosis-necrosis balance Cells Cultured 030304 developmental biology 0303 health sciences Kidney cell culture Chemistry 030302 biochemistry & molecular biology lcsh:R Fibroblasts Ochratoxins Coculture Techniques Cell biology mitochondria medicine.anatomical_structure Gene Expression Regulation Cell culture ochratoxin A Signal Transduction |
Zdroj: | Toxins Volume 13 Issue 3 Toxins, Vol 13, Iss 219, p 219 (2021) |
ISSN: | 2072-6651 |
DOI: | 10.3390/toxins13030219 |
Popis: | The kidney is threatened by a lot of potentially toxic substances. To study the influence of the nephrotoxin ochratoxin A (OTA) we established a cell co-culture model consisting of human renal proximal tubule cells and fibroblasts. We studied the effect of OTA on cell survival, the expression of genes and/or proteins related to cell death, extracellular matrix and energy homeostasis. OTA-induced necrosis was enhanced in both cell types in the presence of the respective other cell type, whereas OTA-induced apoptosis was independent therefrom. In fibroblasts, but not in tubule cells, a co-culture effect was visible concerning the expression of the cell-cycle-related protein p21. The expression of the epithelial-to-mesenchymal transition-indicating protein vimentin was independent from the culture-condition. The expression of the OTA-induced lncRNA WISP1-AS1 was enhanced in co-culture. OTA exposure led to alterations in the expression of genes related to energy metabolism with a glucose-mobilizing effect and a reduced expression of mitochondrial proteins. Together we demonstrate that the reaction of cells can be different in the presence of cells which naturally are close-by, thus enabling a cellular cross-talk. Therefore, to evaluate the toxicity of a substance, it would be an advantage to consider the use of co-cultures instead of mono-cultures. |
Databáze: | OpenAIRE |
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