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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 19, n. 8, p. 15-pg., 2018-08-01.

Resumo

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)

• Processo FAPESP: 15/01630-3 - Papel do sistem chemerin/chemR23 na sinalização da insulina em adipócitos e artérias de camundongos db/db
• Beneficiário: Karla Bianca Neves
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/13144-8 - Efeitos da Adipocina Chemerin Sobre a Responsividade à Insulina de Artérias Mesentéricas de Camundongos
• Beneficiário: Karla Bianca Neves
• Modalidade de apoio: Bolsas no Brasil - Doutorado