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

Neves, Karla Bianca and Montezano, Augusto Cesar and Alves-Lopes, Rheure and Bruder-Nascimento, Thiago and Costa, Rafael Menezes and Costa, Roberto S. and Touyz, Rhian M. and Tostes, Rita 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. ISSN 1661-6596 (https://doi.org/10.3390/ijms19082454)

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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.

ORCID iDs

Neves, Karla Bianca ORCID logoORCID: https://orcid.org/0000-0001-5158-9263, Montezano, Augusto Cesar, Alves-Lopes, Rheure, Bruder-Nascimento, Thiago, Costa, Rafael Menezes, Costa, Roberto S., Touyz, Rhian M. and Tostes, Rita C.;
  • Item type:Article
    ID code:83258
    Dates:
    Date
    Event
    19 August 2018
    Published
    15 August 2018
    Accepted
    Notes:Int. J. Mol. Sci. 2018, 19(8), 2454; https://doi.org/10.3390/ijms19082454 Funding Information: Acknowledgments: We thank ChemoCentryx (Mountain View, CA, USA) for providing the compound CCX832 and consultation; Carla Pavan, Andrew Carswell, Flávio H. Leite and Guilherme P. Lemos for the technical support and help; Aikaterini Anagnostopoulou for her support with the immunofluorescence protocol. We also thank the support from 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). Publisher Copyright: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
    Subjects:Science > Chemistry
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:17 Nov 2022 11:39
    Last modified:11 Nov 2024 13:39
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/83258
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