Advanced oxidation protein products induce epithelial-to-mesenchymal transition in cultured human proximal tubular epithelial cells via oxidative stress / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of advanced oxidation protein products (AOPP) on epithelial-to-mesenchymal transition (EMT) in cultured human proximal tubular epithelial cells (HK-2) and explore the mechanism.</p><p><b>METHODS</b>HK-2 cells treated with 50, 100, 200, and 400 µg/ml AOPP or 50 µg/m bovine serum albumin (BSA) for 24 h, or with 200 µg/ml AOPP for 0.5, 1, 3, 6, 12, and 24 h were examined for the protein expression of α-SMA and E-cadherin. In cells pretreated with diphenyleneiodonium (DPI) or cytoplasmic superoxide dismutase (C-SOD), the effects of 50 µg/ml BSA and 200 µg/ml AOPP were assessed on the expressions of α-SMA and E-cadherin, malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, catalase (CAT) activity, and glutathione peroxidase (GSH-px) activity.</p><p><b>RESULTS</b>AOPP treatment up-regulated α-SMA expression and down-regulated E-cadherin expression in a dose- and time-dependent fashion. AOPP exposure of the cells resulted in increased MDA level and lowered activities of SOD, CAT and GSH-PX. DPI and C-SOD partially attenuated the effects of AOPP on α-SMA, E-cadherin, MDA, SOD, CAT and GSH-px.</p><p><b>CONCLUSION</b>AOPP can induce EMT in cultured HK-2 cells via oxidative stress, and this effect can be attenuated by inhibiting the activation of NADPH oxidase and using antioxidants to delay the progression of renal interstitial fibrosis.</p>