He Ting,Guan Xu,Sun Lei,Yang Ke,Xiao Tangli,Xu Xinli,Yang Qin,Zhao Jinghong.Inhibitory role of resveratrol in high glucose-induced renal tubular epithelia-mesenchymal transition and its underlying mechanism[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(15):1572-1576.
He Ting,Guan Xu,Sun Lei,Yang Ke,Xiao Tangli,Xu Xinli,Yang Qin,Zhao Jinghong.Inhibitory role of resveratrol in high glucose-induced renal tubular epithelia-mesenchymal transition and its underlying mechanism[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(15):1572-1576.DOI:
Inhibitory role of resveratrol in high glucose-induced renal tubular epithelia-mesenchymal transition and its underlying mechanism
Objective To determine the effect of resveratrol on high glucose-induced epithelia-mesenchymal transit
ion (EMT) of renal tubular epithelial cell line HK-2 and its underlying mechanism. Methods Cultured HK-2 cells were divided into 6 groups
that is
normal glucose (NG
5.5 mmol/L)
high glucose (HG
30 mmol/L)
resveratrol (RES
10 μmol/L)
high glucose and resveratrol (HG+RES
30 mmol/L + 10 μmol/L)
diphenyleneiodonium (DPI
NADPH oxdiase inhibitor
10 μmol/L)
and high glucose and DPI group (HG+DPI
30 mmol/L + 10 μmol/L). Inverted microscopy was used to observe the morphological changes in high glucose-induced HK-2 cells. Expression of cytokeratin and vimentin was detected by immunofluorescence assay
and that of of α-smooth muscle actin (α-SMA)
E-cadherin
NADPH oxdiase subunits (NOXs) were measured by Western blotting. Intracellular reactive oxide species (ROS) were detected by DCFH-DA fluorescence probe. Results After incubated with high glucose
HK-2 cells turned into long spindle-shape compared with NG group. Protein levels of epithelial markers E-cadherin and cytokeratin were significantly decreased
while those of the mesenchymal markers α-SMA and vimentin were increased (
P
0.01). Protein levels of NADPH oxidase subunits NOX1 and NOX4 were significantly decreased (
P
0.01)
but that of NOX2 had no change
and intracellular ROS production was significantly increased (1 723.82±303.97 vs 2 579.36±353.76
P
0.01). The pre-incubation of resveratrol or DPI obviously inhibited EMT (
P
0.01) and ROS production (1 803.36±199.54 and 1 837.45±266.83 vs 2 579.36±353.76
P
0.01) in HK-2cells induced by high glucose
while resveratrol markedly inhibited NOX1 and NOX4 expression (
P
0.01). Conclusion Resveratrol may reduce ROS production through suppressing NADPH oxidase in renal epithelial cells
and thus inhibit the EMT of the cells induced by high glucose.