Upregulation of Nrf2 and decreased redox signaling contribute to renoprotective effects of chemerin receptor blockade in diabetic mice

Neves, K. B. , Montezano, A. C., Alves-Lopes, R. , Bruder-Nascimento, T., Costa, R. M., Costa, R. S., Touyz, R. M. and Tostes, R. C. (2018) Upregulation of Nrf2 and decreased redox signaling contribute to renoprotective effects of chemerin receptor blockade in diabetic mice. International Journal of Molecular Sciences, 19(8), 2454. (doi:10.3390/ijms19082454) (PMID:30126255) (PMCID:PMC6121242)

Neves, K. B. , Montezano, A. C., Alves-Lopes, R. , Bruder-Nascimento, T., Costa, R. M., Costa, R. S., Touyz, R. M. and Tostes, R. C. (2018) Upregulation of Nrf2 and decreased redox signaling contribute to renoprotective effects of chemerin receptor blockade in diabetic mice. International Journal of Molecular Sciences, 19(8), 2454. (doi:10.3390/ijms19082454) (PMID:30126255) (PMCID:PMC6121242)

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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.

Item Type:Articles
Additional Information:Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP grants 2012/13144-8 and 2015/01630-3 to KBN, and 2013/08216-2 to the Center of Research in Inflammatory Diseases—CRID), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES 2053-13-6), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMT is supported by a British Heart Foundation Chair (CH/12/429762).
Keywords:Kidney, oxidative stress, type 2 diabetes, chemerin, Chemr23.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lopes, Dr Rheure and Montezano, Dr Augusto and Touyz, Professor Rhian and Neves, Dr Karla Bianca
Authors: Neves, K. B., Montezano, A. C., Alves-Lopes, R., Bruder-Nascimento, T., Costa, R. M., Costa, R. S., Touyz, R. M., and Tostes, R. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:International Journal of Molecular Sciences
Publisher:MDPI
ISSN:1661-6596
ISSN (Online):1422-0067
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in International Journal of Molecular Sciences 19(8):2454
Publisher Policy:Reproduced under a Creative Commons License

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