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

被引：43
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
收藏
页数：12
相关论文
共 42 条
[1]   Eye-Light on Age-Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy for Retinal Pigment Epithelium [J].
Catanzaro, Michele ;
Lanni, Cristina ;
Basagni, Filippo ;
Rosini, Michela ;
Govoni, Stefano ;
Amadio, Marialaura .
FRONTIERS IN PHARMACOLOGY, 2020, 11
[2]   Anti-Inflammatory and Anti-Oxidative Effects of luteolin-7-O-glucuronide in LPS-Stimulated Murine Macrophages through TAK1 Inhibition and Nrf2 Activation [J].
Cho, Young-Chang ;
Park, Jiyoung ;
Cho, Sayeon .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (06)
[3]   Prevalence of Age-Related Macular Degeneration in Europe [J].
Colijn, Johanna M. ;
Buitendijk, Gabrielle H. S. ;
Prokofyeva, Elena ;
Alves, Dalila ;
Cachulo, Maria L. ;
Khawaja, Anthony P. ;
Cougnard-Gregoire, Audrey ;
Merle, Benedicte M. J. ;
Korb, Christina ;
Erke, Maja G. ;
Bron, Alain ;
Anastasopoulos, Eleftherios ;
Meester-Smoor, Magda A. ;
Segato, Tatiana ;
Piermarocchi, Stefano ;
de Jong, Paulus T. V. M. ;
Vingerling, Johannes R. ;
Topouzis, Fotis ;
Creuzot-Garcher, Catherine ;
Bertelsen, Geir ;
Pfeiffer, Norbert ;
Fletcher, Astrid E. ;
Foster, Paul J. ;
Silva, Rufino ;
Korobelnik, Jean-Francois ;
Delcourt, Cecile ;
Klaver, Caroline C. W. .
OPHTHALMOLOGY, 2017, 124 (12) :1753-1763
[4]   Melatonin prevents LPS-induced epithelial-mesenchymal transition in human alveolar epithelial cells via the GSK-3β/Nrf2 pathway [J].
Ding, Zhenxing ;
Wu, Xu ;
Wang, Yueguo ;
Ji, Shuang ;
Zhang, Wenying ;
Kang, Jiaying ;
Li, Jiajia ;
Fei, Guanghe .
BIOMEDICINE & PHARMACOTHERAPY, 2020, 132
[5]   Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration [J].
Felszeghy, Szabolcs ;
Viiri, Johanna ;
Paterno, Jussi J. ;
Hyttinen, Juha M. T. ;
Koskela, Ali ;
Chen, Mei ;
Leinonen, Henri ;
Tanila, Heikki ;
Kivinen, Niko ;
Koistinen, Arto ;
Toropainen, Elisa ;
Amadio, Marialaura ;
Smedowski, Adrian ;
Reinisalo, Mika ;
Winiarczyk, Mateusz ;
Mackiewicz, Jerzy ;
Mutikainen, Maija ;
Ruotsalainen, Anna-Kaisa ;
Kettunen, Mikko ;
Jokivarsi, Kimmo ;
Sinha, Debasish ;
Kinnunen, Kati ;
Petrovski, Goran ;
Blasiak, Janusz ;
Bjorkoy, Geir ;
Koskelainen, Ari ;
Skottman, Heli ;
Urtti, Arto ;
Salminen, Antero ;
Kannan, Ram ;
Ferrington, Deborah A. ;
Xu, Heping ;
Levonen, Anna-Liisa ;
Tavi, Pasi ;
Kauppinen, Anu ;
Kaarniranta, Kai .
REDOX BIOLOGY, 2019, 20 :1-12
[6]   Diosmetin prevents TGF-β1-induced epithelial-mesenchymal transition via ROS/MAPK signaling pathways [J].
Ge, Ai ;
Ma, Yuan ;
Liu, Ya-Nan ;
Li, Ye-Shan ;
Gu, Hao ;
Zhang, Jia-Xiang ;
Wang, Qin-Xue ;
Zeng, Xiao-Ning ;
Huang, Mao .
LIFE SCIENCES, 2016, 153 :1-8
[7]   Signaling mechanisms of the epithelial-mesenchymal transition [J].
Gonzalez, David M. ;
Medici, Damian .
SCIENCE SIGNALING, 2014, 7 (344) :re8
[8]   Hydrogen sulfide attenuates cigarette smoke-induced airway remodeling by upregulating SIRT1 signaling pathway [J].
Guan, Ruijuan ;
Wang, Jian ;
Cai, Zhou ;
Li, Ziying ;
Wang, Lan ;
Li, Yuanyuan ;
Xu, Jingyi ;
Li, Defu ;
Yao, Hongwei ;
Liu, Wei ;
Deng, Bingxian ;
Lu, Wenju .
REDOX BIOLOGY, 2020, 28
[9]  
Guidry C, 2002, INVEST OPHTH VIS SCI, V43, P267
[10]   How does the macula protect itself from oxidative stress? [J].
Handa, James T. .
MOLECULAR ASPECTS OF MEDICINE, 2012, 33 (04) :418-435
12345