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

AI Article Synopsis

Article Abstract

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 HO-induced EMT in ARPE-19 cells. ARPE-19 cells were incubated with HO at 200  to induce oxidative stress-associated injury. Cell viability assay showed that luteolin at 20 and 40 M significantly promoted cell survival in HO-treated ARPE-19 cells. Luteolin also markedly protected ARPE-19 cells from HO-induced apoptosis. Cell migration assay presented that luteolin significantly reduced HO-induced migration in APRE-19 cells. EMT in ARPE-19 cells was detected by western blotting and immunofluorescence. The results showed that HO significantly upregulated the expression of -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 HO-treated ARPE-19 cells. Meanwhile, we observed that the expression of TGF-2, p-AKT, and p-GSK-3 was upregulated in HO-treated ARPE-19 cells and downregulated in luteolin-treated cells, revealing that luteolin inhibited the activation of the AKT/GSK-3 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 pathway, suggesting that luteolin could be a potential drug for the treatment of dry AMD.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860553PMC
http://dx.doi.org/10.1155/2022/2265725DOI Listing

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