Ochratoxin A (OTA) is a toxin produced by fungi such as Aspergillus spp. and Penicillium spp. The key target organ of OTA toxicity is the kidney, and it is known that epithelial-to-mesenchymal transition (EMT) leading to fibrosis is enhanced after long-term exposure of the kidney to OTA. However, the mechanisms responsible for this onset are not precisely known. Therefore, the purpose of this study was to investigate the mechanism of OTA-induced EMT and fibrosis in human proximal tubule HK-2 cells and mouse kidneys. Cells were treated for 48 h with various concentrations of OTA (50, 100, and 200 nM) and mice underwent oral administration of various doses of OTA (200 and 1000 μg/kg body weight) for 12 weeks. Blood urea nitrogen and creatinine levels were increased in the serum of OTA-treated mice, and fibrosis was observed in kidney tissues. Furthermore, alpha-smooth muscle actin (α-SMA) and fibronectin levels were increased, and E-cadherin level was decreased by OTA in both HK-2 cells and kidney tissues. In addition, the expression levels of TGF-β, smad2/3, and β-catenin were increased after OTA treatment. α-SMA, E-cadherin, and fibronectin were shown to be regulated by the activation of transcription factors, smad2/3 and β-catenin. These results demonstrated that OTA induces EMT and renal fibrosis through Smad2/3 and β-catenin signaling pathways in vitro and in vivo.

ch曲毒素A（OTA）是由真菌（如曲霉属）产生的毒素。和青霉属。OTA毒性的主要靶器官是肾脏，众所周知，肾脏长期暴露于OTA后，导致纤维化的上皮-间质转化（EMT）会增强。但是，导致这种发作的机制尚不清楚。因此，本研究的目的是研究OTA诱导人近端肾小管HK-2细胞和小鼠肾脏中EMT和纤维化的机制。将细胞用各种浓度的OTA（50、100和200 nM）处理48小时，然后对小鼠口服各种剂量的OTA（200和1000μg/ kg体重），持续12周。OTA处理的小鼠血清中的血尿素氮和肌酐水平升高，并且在肾组织中观察到纤维化。此外，α平滑肌肌动蛋白（α-SMA）和纤连蛋白水平增加，OTA降低了HK-2细胞和肾脏组织中的E-钙粘蛋白水平。另外，OTA处理后，TGF-β，smad2 / 3和β-catenin的表达水平升高。已证明α-SMA，E-钙黏着蛋白和纤连蛋白受转录因子smad2 / 3和β-catenin的激活调节。这些结果表明，OTA通过Smad2 / 3和β-catenin信号传导途径在体内和体外诱导EMT和肾纤维化。