[Advanced oxidation protein products induce epithelial-to-mesenchymal transition in cultured human proximal tubular epithelial cells via oxidative stress].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. E-mail: gzh_zj@qq.com.
Jun
J
Zhang
Minzi
M
Qiu
Yaqiong
Y
Ma
Yang
Y
Bu
Lei
L
Yang
Xun
X
Tang
D000199:Actins / Q000378:metabolism; D062107:Advanced Oxidation Protein Products; D015703:Antigens, CD; D000975:Antioxidants / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
D000199:Actins; D062107:Advanced Oxidation Protein Products; D015703:Antigens, CD; D000975:Antioxidants; C513384:CDH1 protein, human; D015820:Cadherins; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases