Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice
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 s...
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doaj-d96c05e229e5430c8db9d01a3fdd797e2020-11-24T21:08:44ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-08-01198245410.3390/ijms19082454ijms19082454Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic MiceKarla Bianca Neves0Augusto Cesar Montezano1Rheure Alves-Lopes2Thiago Bruder-Nascimento3Rafael Menezes Costa4Roberto S Costa5Rhian M Touyz6Rita C Tostes7Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, BrazilInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UKDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, BrazilDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, BrazilDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, BrazilDepartment of Pathology and Legal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, BrazilInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UKDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, BrazilChemerin, 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.http://www.mdpi.com/1422-0067/19/8/2454chemerinChemR23kidneytype 2 diabetesoxidative stress |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karla Bianca Neves Augusto Cesar Montezano Rheure Alves-Lopes Thiago Bruder-Nascimento Rafael Menezes Costa Roberto S Costa Rhian M Touyz Rita C Tostes |
spellingShingle |
Karla Bianca Neves Augusto Cesar Montezano Rheure Alves-Lopes Thiago Bruder-Nascimento Rafael Menezes Costa Roberto S Costa Rhian M Touyz Rita C Tostes Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice International Journal of Molecular Sciences chemerin ChemR23 kidney type 2 diabetes oxidative stress |
author_facet |
Karla Bianca Neves Augusto Cesar Montezano Rheure Alves-Lopes Thiago Bruder-Nascimento Rafael Menezes Costa Roberto S Costa Rhian M Touyz Rita C Tostes |
author_sort |
Karla Bianca Neves |
title |
Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice |
title_short |
Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice |
title_full |
Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice |
title_fullStr |
Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice |
title_full_unstemmed |
Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice |
title_sort |
upregulation of nrf2 and decreased redox signaling contribute to renoprotective effects of chemerin receptor blockade in diabetic mice |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-08-01 |
description |
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. |
topic |
chemerin ChemR23 kidney type 2 diabetes oxidative stress |
url |
http://www.mdpi.com/1422-0067/19/8/2454 |
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