Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Environ Toxicol. 2022 Aug;37(8):2084-2095. doi: 10.1002/tox.23552. Epub 2022 May 11.
Ochratoxin A (OTA) is a mycotoxin generated by Penicillium and Aspergillus species. It is often found in cereals. We hypothesized that OTA exposure induces epithelial-mesenchymal transition (EMT), leading to liver fibrosis. In this research, we explored whether the TGF-β receptor I (TGF-β RI)/Smad2/3 signaling pathway is related to EMT-induced hepatic fibrosis. In vitro and in vivo experiments, mRNA and protein expression of liver fibrosis-related markers such as fibronectin, α-smooth muscle actin (α-SMA) and E-cadherin were assessed. The levels of alkaline phosphatase, alanine transaminase, aspartate aminotransferase, and total bilirubin, which are used to assess damage, increased. We also confirmed the increase in mRNA and protein expression of TGF-β RI, Smad2, and Smad3. The expression of liver fibrosis-related markers was decreased by siRNA-mediated silencing of Smad2/3, as well as TGF-RI suppression. Liver cells exposed to OTA showed enhanced TGF-β RI expression on the cell membrane. These results demonstrated that OTA induces hepatic fibrosis through TGF-β RI and Smad2/3 pathways in vitro and in vivo.
赭曲霉毒素 A（OTA）是由青霉和曲霉属物种产生的一种真菌毒素。它通常存在于谷物中。我们假设 OTA 暴露会诱导上皮-间充质转化（EMT），导致肝纤维化。在这项研究中，我们探讨了 TGF-β 受体 I（TGF-β RI）/Smad2/3 信号通路是否与 EMT 诱导的肝纤维化有关。通过体外和体内实验，评估了纤维化相关标志物如纤连蛋白、α-平滑肌肌动蛋白（α-SMA）和 E-钙黏蛋白的 mRNA 和蛋白表达。用于评估损伤的碱性磷酸酶、丙氨酸转氨酶、天冬氨酸转氨酶和总胆红素水平也升高了。我们还证实了 TGF-β RI、Smad2 和 Smad3 的 mRNA 和蛋白表达增加。通过 siRNA 介导的 Smad2/3 沉默以及 TGF-RI 抑制，纤维化相关标志物的表达减少。OTA 处理的肝细胞在细胞膜上显示出增强的 TGF-β RI 表达。这些结果表明，OTA 在体外和体内通过 TGF-β RI 和 Smad2/3 途径诱导肝纤维化。
