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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Neves, Karla Bianca [1, 2, 3] ; Montezano, Augusto Cesar [2] ; Alves-Lopes, Rheure [2] ; Bruder-Nascimento, Thiago [1] ; Costa, Rafael Menezes [1] ; Costa, Roberto S. [4] ; Touyz, Rhian M. [2] ; Tostes, Rita C. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Ribeirao Preto - Brazil
[2] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark - Scotland
[3] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040093 Ribeirao Preto - Brazil
[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol & Legal Med, BR-14040900 Ribeirao Preto - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 19, n. 8 AUG 2018.
Citações Web of Science: 3
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
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
Processo FAPESP: 12/13144-8 - Efeitos da adipocina Chemerin sobre a responsividade à insulina de artérias mesentéricas de camundongos
Beneficiário:Karla Bianca Neves
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs