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

Abstract

N^ε-(carboxymethyl) lysine (CML) plays causal roles in diabetic complications. In the present study, we investigated whether CML-induced HIF-1α 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, α-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-1α (HIF-1α), and the EMT-associated transcription factor, TWIST. These effects were reversed by α-lipoic acid. CML-BSA increased the protein levels of mesenchymal-specific markers, including vimentin, α-smooth muscle actin, which were alleviated by pre-treatment with α-lipoic acid. Our data suggest that CML-BSA induces EMT through a ROS/HIF-1α/TWIST-dependent mechanism, and that α-lipoic acid may alleviate the CML-induced EMT in renal tubular cells.

Keywords:

• EMT
• HIF-1α
• mitochondria
• N^ε-(carboxymethyl) lysine
• TWIST

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the research grant from the Ministry of Science and Technology [MOST106-2320-B-038-043 for HML].