{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:47:19Z","timestamp":1790660839552,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T00:00:00Z","timestamp":1522886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>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-\u03b21 (TGF-\u03b21), 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-\u03b21 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.<\/jats:p>","DOI":"10.3390\/md16040117","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T16:50:58Z","timestamp":1522947058000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Astaxanthin Promotes Nrf2\/ARE Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs"],"prefix":"10.3390","volume":"16","author":[{"given":"Qing","family":"Chen","sequence":"first","affiliation":[{"name":"Hainan Key Laboratory of Sustainable Utilization of Tropical Bioresources, Hainan University, Haikou 570228, China"},{"name":"School of Life Science, Institute of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9046-0283","authenticated-orcid":false,"given":"Jun","family":"Tao","sequence":"additional","affiliation":[{"name":"Hainan Key Laboratory of Sustainable Utilization of Tropical Bioresources, Hainan University, Haikou 570228, China"},{"name":"School of Life Science, Institute of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Xie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou 570228, China"},{"name":"Hainan Provincial Key Laboratory for Tropical Hydrobiology and Biotechnology, College of Marine Science, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev.pathol.4.110807.092150","article-title":"A glimpse of various pathogenetic mechanisms of diabetic nephropathy","volume":"6","author":"Kanwar","year":"2011","journal-title":"Annu. 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