Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice

• Published in: International journal of molecular sciences 2018-08, Vol.19 (8), p.2454
• Main Authors: Neves, Karla Bianca, Montezano, Augusto Cesar, Alves-Lopes, Rheure, Bruder-Nascimento, Thiago, Costa, Rafael Menezes, Costa, Roberto S, Touyz, Rhian M, Tostes, Rita C
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Cancer; chemerin; Chemokines; ChemR23; Dendritic cells; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic Nephropathies - prevention & control; Diabetic nephropathy; Gene expression; Glucose; Glucose metabolism; Inflammation; Inflammatory response; Insulin resistance; kidney; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidneys; Legal medicine; Lipid metabolism; Lipids; Male; Metabolism; Mice; Mice, Inbred C57BL; Musculoskeletal system; Nephropathy; NF-E2-Related Factor 2 - metabolism; Obesity; Oxidation; Oxidation-Reduction - drug effects; Oxidative stress; Oxidative Stress - drug effects; Proteins; Reactive oxygen species; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - metabolism; Redox properties; Renal function; Rodents; type 2 diabetes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19082454

Chemerin, acting through its receptor ChemR23, is an adipokine associated with inflammatory response, glucose and lipid metabolism and vascular function. Although this adipokine has been associated with the development and progression of kidney disease, it is not clear whether the chemerin/ChemR23 system plays a role in renal function in the context of diabetes. Therefore, we sought to determine whether ChemR23 receptor blockade prevents the development and/or progression of diabetic nephropathy and questioned the role of oxidative stress and Nrf2 in this process. Renal redox state and function were assessed in non-diabetic lean db/m and diabetic obese db/db mice treated with vehicle or CCX832 (ChemR23 antagonist). Renal reactive oxygen species (ROS) production, which was increased in diabetic mice, was attenuated by CCX832. This was associated with an increase in Nox 4 expression. Augmented protein oxidation in db/db mice was not observed when mice were treated with CCX832. also abrogated impaired Nrf2 nuclear activity and associated downregulation in antioxidants expression in kidneys from db/db mice. Our in vivo findings highlight the role of the redox signaling and Nrf2 system as renoprotective players during chemerin receptor blockade in diabetic mice. The chemerin/ChemR23 system may be an important target to limit renal dysfunction associated with obesity-related diabetes.