Luteolin Alleviates Epithelial-Mesenchymal Transformation Induced by Oxidative Injury in ARPE-19 Cell via Nrf2 and AKT/GSK-3β Pathway

被引：44

作者：

Chen, Lan ^{[1
]}

Zhu, Yanqing ^{[1
]}

Zhou, Jie ^{[1
]}

Wu, Rui ^{[1
]}

Yang, Ning ^{[1
]}

Bao, Qinbin ^{[1
]}

Xu, Xinrong ^{[1
]}

机构：

[1] Nanjing Univ Chinese Med, Affiliated Hosp, Jiangsu Prov Hosp Chinese Med, Dept Ophthalmol, Nanjing 210029, Peoples R China

来源：

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY | 2022年 / 2022卷

基金：

中国国家自然科学基金;

关键词：

RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; PREVALENCE; TRANSITION;

D O I：

10.1155/2022/2265725

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Oxidative stress plays a critical role in age-related macular degeneration (AMD), and epithelial-mesenchymal transition (EMT) is involved in this process. The aim of this study was to investigate the protective effects of luteolin, a natural flavonoid with strong antioxidant activity, on H2O2-induced EMT in ARPE-19 cells. ARPE-19 cells were incubated with H2O2 at 200 mu M to induce oxidative stress-associated injury. Cell viability assay showed that luteolin at 20 and 40 mu M significantly promoted cell survival in H2O2-treated ARPE-19 cells. Luteolin also markedly protected ARPE-19 cells from H2O2-induced apoptosis. Cell migration assay presented that luteolin significantly reduced H2O2-induced migration in APRE-19 cells. EMT in ARPE-19 cells was detected by western blotting and immunofluorescence. The results showed that H2O2 significantly upregulated the expression of alpha-SMA and vimentin and downregulated the expression of ZO-1 and E-cadherin, while cells pretreated with luteolin showed a reversal. Meanwhile, the assessment of effects of luteolin on the Nrf2 pathway indicated that luteolin promoted Nrf2 nuclear translocation and upregulated the expressions of HO-1 and NQO-1. In addition, luteolin significantly increased the activities of SOD and GSH-PX and decreased intracellular levels of ROS and MDA in H2O2-treated ARPE-19 cells. Meanwhile, we observed that the expression of TGF-beta 2, p-AKT, and p-GSK-3 beta was upregulated in H2O2-treated ARPE-19 cells and downregulated in luteolin-treated cells, revealing that luteolin inhibited the activation of the AKT/GSK-3 beta pathway. However, these effects of luteolin were all annulled by transfecting ARPE-19 cells with Nrf2 siRNA. Our current data collectively indicated that inhibition of luteolin on EMT was induced by oxidative injury in ARPE-19 cell through the Nrf2 and AKT/GSK-3 beta pathway, suggesting that luteolin could be a potential drug for the treatment of dry AMD.

引用

页数：12

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