Astaxanthin Promotes Nrf2/ARE Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs

被引:69
作者
Chen, Qing [1 ,2 ]
Tao, Jun [1 ,2 ]
Xie, Xi [3 ,4 ]
机构
[1] Hainan Univ, Hainan Key Lab Sustainable Utilizat Trop Bioresou, Haikou 570228, Hainan, Peoples R China
[2] Hainan Univ, Inst Trop Agr & Forestry, Sch Life Sci, Haikou 570228, Hainan, Peoples R China
[3] Hainan Univ, Minist Educ, Key Lab Trop Biol Resources, Haikou 570228, Hainan, Peoples R China
[4] Hainan Univ, Coll Marine Sci, Hainan Prov Key Lab Trop Hydrobiol & Biotechnol, Haikou 570228, Hainan, Peoples R China
基金
中国国家自然科学基金;
关键词
astaxanthin; oxidative stress; renal fibrosis; diabetic nephropathy; Nrf2/ARE signaling; INDUCED DIABETIC-NEPHROPATHY; GLYCATION END-PRODUCTS; OXIDATIVE STRESS; MESANGIAL CELLS; GENE-EXPRESSION; KIDNEY-DISEASE; PATHWAY; ACTIVATION; INFLAMMATION; MECHANISMS;
D O I
10.3390/md16040117
中图分类号
R914 [药物化学];
学科分类号
100705 [微生物与生化药学];
摘要
Oxidative stress is the main cause of diabetic nephropathy (DN) progression. Nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling is a crucial cellular defense system to cope with oxidative stress. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid with remarkable antioxidative capacity. AST exerted renal protective in diabetic rats. This study aimed to determine whether AST could alleviate the pathological progress of DN by activating Nrf2/ARE signaling and diminishing the excessive oxidative stress and fibronectin (FN) accumulation in glomerular mesangial cells (GMCs) challenged with high glucose (HG). In the current study, we found that AST treatment alleviated the metabolic parameters, renal morphology and extracellular matrix (ECM) accumulation in streptozotocin-induced diabetic rats. Additionally, HG induced the adaptively activated Nrf2/ARE signaling and increased the expression of FN, intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-beta 1), as well as the intracellular reactive oxygen species (ROS) generation in GMCs. However, AST treatment strongly promoted the nuclear translocation and transcriptional activity of Nrf2 as well as upregulated the expression of superoxide dismutase (SOD1), NAD(P)H: quinone oxidoreductase (NQO1) and heme oxygenase-1 (HO-1), ultimately quenching the higher level of ROS and inhibiting the FN, ICAM-1 and TGF-beta 1 expression induced by HG. Collectively, our data suggest that the renoprotective effect of AST on DN depends on Nrf2/ARE signaling activation, which could be a potentially therapeutic strategy in the treatment of DN.
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页数:17
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