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Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage
Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM). This study aimed to explore the effects of corosolic acid (CA) on the renal damage of DM and the mechanisms behind these effects. The renoprotective effect of CA was investigated in type 1 diabetic rats and db/db...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882506/ https://www.ncbi.nlm.nih.gov/pubmed/27229751 http://dx.doi.org/10.1038/srep26854 |
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author | Li, Xiao-Qiang Tian, Wen Liu, Xiao-Xiao Zhang, Kai Huo, Jun-Cheng Liu, Wen-Juan Li, Ping Xiao, Xiong Zhao, Ming-Gao Cao, Wei |
author_facet | Li, Xiao-Qiang Tian, Wen Liu, Xiao-Xiao Zhang, Kai Huo, Jun-Cheng Liu, Wen-Juan Li, Ping Xiao, Xiong Zhao, Ming-Gao Cao, Wei |
author_sort | Li, Xiao-Qiang |
collection | PubMed |
description | Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM). This study aimed to explore the effects of corosolic acid (CA) on the renal damage of DM and the mechanisms behind these effects. The renoprotective effect of CA was investigated in type 1 diabetic rats and db/db mice. The kidneys and glomerular mesangial cells (GMCs) were used to study the proliferation of GMCs by immunostaining and MTT assay. Further immunoblotting, siRNA, qPCR analysis, and detecting of NADPH oxidase activity and reactive oxygen species (ROS) generation were performed to explore relevant molecular mechanisms. In CA-treated diabetic animals, diabetes-induced albuminuria, increased serum creatinine and blood urea nitrogen were significantly attenuated, and glomerular hypertrophy, mesangial expansion and fibrosis were ameliorated. Furthermore, CA significantly inhibited proliferation of GMCs and phosphorylation of ERK1/2 and p38 MAPK in both diabetic animals and high glucose (HG)-induced GMCs. CA also normalized Δψm and inhibited HG-induced NADPH oxidase activity, ROS generation and NOX4, NOX2, p22(phox) and p47(phox) expression. More importantly, CA inhibited GMC proliferation mediated by NADPH/ERK1/2 and p38 MAPK signaling pathways. These findings suggest that CA exert the protective effect on DN by anti-proliferation resulted from inhibition of p38 MAPK- and NADPH-mediated inactivation of ERK1/2. |
format | Online Article Text |
id | pubmed-4882506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48825062016-06-08 Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage Li, Xiao-Qiang Tian, Wen Liu, Xiao-Xiao Zhang, Kai Huo, Jun-Cheng Liu, Wen-Juan Li, Ping Xiao, Xiong Zhao, Ming-Gao Cao, Wei Sci Rep Article Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM). This study aimed to explore the effects of corosolic acid (CA) on the renal damage of DM and the mechanisms behind these effects. The renoprotective effect of CA was investigated in type 1 diabetic rats and db/db mice. The kidneys and glomerular mesangial cells (GMCs) were used to study the proliferation of GMCs by immunostaining and MTT assay. Further immunoblotting, siRNA, qPCR analysis, and detecting of NADPH oxidase activity and reactive oxygen species (ROS) generation were performed to explore relevant molecular mechanisms. In CA-treated diabetic animals, diabetes-induced albuminuria, increased serum creatinine and blood urea nitrogen were significantly attenuated, and glomerular hypertrophy, mesangial expansion and fibrosis were ameliorated. Furthermore, CA significantly inhibited proliferation of GMCs and phosphorylation of ERK1/2 and p38 MAPK in both diabetic animals and high glucose (HG)-induced GMCs. CA also normalized Δψm and inhibited HG-induced NADPH oxidase activity, ROS generation and NOX4, NOX2, p22(phox) and p47(phox) expression. More importantly, CA inhibited GMC proliferation mediated by NADPH/ERK1/2 and p38 MAPK signaling pathways. These findings suggest that CA exert the protective effect on DN by anti-proliferation resulted from inhibition of p38 MAPK- and NADPH-mediated inactivation of ERK1/2. Nature Publishing Group 2016-05-27 /pmc/articles/PMC4882506/ /pubmed/27229751 http://dx.doi.org/10.1038/srep26854 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Li, Xiao-Qiang Tian, Wen Liu, Xiao-Xiao Zhang, Kai Huo, Jun-Cheng Liu, Wen-Juan Li, Ping Xiao, Xiong Zhao, Ming-Gao Cao, Wei Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage |
title | Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage |
title_full | Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage |
title_fullStr | Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage |
title_full_unstemmed | Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage |
title_short | Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage |
title_sort | corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882506/ https://www.ncbi.nlm.nih.gov/pubmed/27229751 http://dx.doi.org/10.1038/srep26854 |
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