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

Author(s)

Neves, Karla Bianca ; Montezano, Augusto Cesar ; Alves-Lopes, Rheure ; Bruder-Nascimento, Thiago ; Costa, Rafael Menezes ; Costa, Roberto S. ; Touyz, Rhian M. ; Tostes, Rita C.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 19, n. 8, p. 15-pg., 2018-08-01.

Abstract

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. 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. (AU)

• FAPESP's process: 15/01630-3 - Role of chemerin/ChemR23 system on insulin signalling in adipocytes and arteries of db/db mice
• Grantee: Karla Bianca Neves
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/13144-8 - Effects of the adipokine Chemerin on the Responsiveness to Insulin Mesenteric Arteries of Mice
• Grantee: Karla Bianca Neves
• Support Opportunities: Scholarships in Brazil - Doctorate