Julius-Bernstein-Institut für Physiologie, 06112 Halle, Germany.
Toxins (Basel). 2021 Mar 18;13(3):219. doi: 10.3390/toxins13030219.
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.
肾脏受到许多潜在有毒物质的威胁。为了研究肾毒素赭曲霉毒素 A (OTA) 的影响，我们建立了一个由人肾近端小管细胞和成纤维细胞组成的细胞共培养模型。我们研究了 OTA 对细胞存活、与细胞死亡、细胞外基质和能量稳态相关的基因和/或蛋白表达的影响。在存在相应的另一种细胞类型的情况下，两种细胞类型中的 OTA 诱导的坏死均增强，而 OTA 诱导的凋亡则与之无关。在成纤维细胞中，但在小管细胞中，与细胞周期相关蛋白 p21 的表达有关的共培养效应是可见的。上皮-间充质转化指示蛋白波形蛋白的表达与培养条件无关。OTA 诱导的 lncRNA WISP1-AS1 的表达在共培养中增强。OTA 暴露导致与能量代谢相关的基因表达发生改变，具有葡萄糖动员作用和线粒体蛋白表达减少。综上所述，我们证明了在存在天然相邻细胞的情况下，细胞的反应可能不同，从而实现细胞间通讯。因此，为了评估一种物质的毒性，考虑使用共培养而不是单一培养将是一个优势。
