Alpha-lipoic acid suppresses N ε -(carboxymethyl) lysine-induced epithelial mesenchymal transition in HK-2 human renal proximal tubule cells

摘要

N ?-(carboxymethyl) lysine (CML) plays causal roles in diabetic complications. In the present study, we investigated whether CML-induced HIF-1?accumulation and epithelial-mesenchymal transition (EMT) in HK-2 renal proximal tubular epithelial cells. Treatment with CML-BSA increased reactive oxygen species (ROS) production reduced the mitochondrial membrane potential and induced mitochondrial fragmentation. Pre-treatment of cells with antioxidant, ?lipoic acid, normalised the ROS production and restored the mitochondrial membrane potential. These changes were accompanied with morphological changes of epithelial mesenchymal transition. CML-BSA increased the protein level of hypoxia-inducible factor-1?(HIF-1?, and the EMT-associated transcription factor, TWIST. These effects were reversed by ?lipoic acid. CML-BSA increased the protein levels of mesenchymal-specific markers, including vimentin, ?smooth muscle actin, which were alleviated by pre-treatment with ?lipoic acid. Our data suggest that CML-BSA induces EMT through a ROS/HIF-1?TWIST-dependent mechanism, and that ?lipoic acid may alleviate the CML-induced EMT in renal tubular cells. ?2019, ?2019 Informa UK Limited, trading as Taylor & Francis Group.