ArticleDiabetologia2016
C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 100 citations in OpenAlex.
- Potential Involvement of Redox and Inflammatory Signalling in the Antihyperglycemic and Antioxidant Effects of Harmaline in Male Mice With Type 2 Diabetes.Endocrinology, diabetes & metabolism · 2026Article
- Dual role of miR-21-enriched MSC-derived exosomes in diabetic nephropathy: therapeutic potential versus p53-driven pathogenicity.BMC nephrology · 2026Article
- Phenolic compounds and epigenetic mechanisms regulating gene expression: effects on human health.Journal of physiology and biochemistry · 2025Review
- [Diabetic Nephropathy Treatment by Zn Supplementation in a Murine Model of Type 1 Diabetes Mellitus: Potential Role of Nrf2 Signaling Pathway].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Curcumin mediates oxidative stress to play an anti-fibrotic role, focusing on liver, renal, myocardial and pulmonary fibrosis.Frontiers in pharmacology · 2025Review
- Repurposing Nano Curcumin: Unveiling its Therapeutic Potential in Diabetic Nephropathy.Current drug targets · 2025Review
- miR-141-3p attenuates inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway.Immunologic research · 2024Article
- Molecular Therapeutics for Diabetic Kidney Disease: An Update.International journal of molecular sciences · 2024Review
- The implication of miR-200a and miR-132 expression and their correlations with NF-κB/TNF-alpha signaling in adults with diabetic nephropathy.Saudi journal of biological sciences · 2024Article
- Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia.Antioxidants (Basel, Switzerland) · 2023Review
- Antidiabetic Effect of Collagen Peptides fromMarine drugs · 2023Article
- Kidney fibrosis: from mechanisms to therapeutic medicines.Signal transduction and targeted therapy · 2023Review
- Sestrin2 Signaling Pathway Regulates Podocyte Biology and Protects against Diabetic Nephropathy.Journal of diabetes research · 2023Review
- NRF2 and Diabetes: The Good, the Bad, and the Complex.Diabetes · 2022Review
- Review
- Efficacy of the monocarbonyl curcumin analog C66 in the reduction of diabetes-associated cardiovascular and kidney complications.Molecular medicine (Cambridge, Mass.) · 2022Review
- Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives.Biomolecules · 2022Review
- Krill Oil Inhibits NLRP3 Inflammasome Activation in the Prevention of the Pathological Injuries of Diabetic Cardiomyopathy.Nutrients · 2022Article
- Comprehensive overview of Nrf2-related epigenetic regulations involved in ischemia-reperfusion injury.Theranostics · 2022Review
- MicroRNA-21: A Critical Pathogenic Factor of Diabetic Nephropathy.Frontiers in endocrinology · 2022Review
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
aims/hypothesisDiabetic nephropathy is the leading cause of end-stage renal disease. Previously we reported that C66, a novel analogue of curcumin with a very high bioavailability, ameliorated diabetic nephropathy in mice, with little known about the mechanism. The present study aimed to define the mechanism by which C66 ameliorates diabetic nephropathy.
methodsOur aim was to discover whether C66 acts through the activation of nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2), which governs the antioxidant response. Streptozotocin-induced Nrf2 (also known as Nfe2l2)-knockout and wild-type (WT) diabetic mice were treated with C66. To determine whether the actions of C66 on NRF2 are mediated by microRNA (miR)-200a, WT diabetic mice were treated with C66 in the presence or absence of an in vivo miR-200a inhibitor (locked nucleic acid-modified anti-miR-200a [LNA-200a]) for 6 months. To determine whether miR-21 downregulation provided an NRF2-independent basis for C66 protection, Nrf2-knockout diabetic mice were treated with either C66 or an inhibitor of miR-21 (locked nucleic acid-modified anti-miR-21 [LNA-21]).
resultsDeletion of Nrf2 partially abolished diabetic nephropathy protection by C66, confirming the requirement of NRF2 for this protection. Diabetic mice, but not C66-treated diabetic mice, developed significant albuminuria, renal oxidative damage and fibrosis. C66 upregulated renal miR-200a, inhibited kelch-like ECH-associated protein 1 and induced NRF2 function, effects that were prevented by LNA-200a. However, LNA-200a only partially reduced the protection afforded by C66, suggesting the existence of miR-200a/NRF2-independent mechanisms for C66 protection. C66 was also found to inhibit diabetes induction of miR-21. Both C66 and LNA-21 produced similar reductions in miR-21, albuminuria and renal fibrosis. CONCLUSIONS/
interpretationThe present study indicates that in addition to upregulating NRF2 by increasing miR-200a, C66 also protects against diabetic nephropathy by inhibiting miR-21.
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