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Smad7 protects against chronic aristolochic acid nephropathy in mice
Chronic Aristolochic Acid Nephropathy (AAN) is a progressive chronic kidney disease related to herb medicine. However, treatment for chronic AAN remains ineffective. We report here that Smad7 is protective and has therapeutic potential for chronic AAN. In a mouse model of chronic AAN, progressive re...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494914/ https://www.ncbi.nlm.nih.gov/pubmed/25883225 |
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author | Dai, Xiao-Yu Zhou, Li Huang, Xiao-Ru Fu, Ping Lan, Hui-Yao |
author_facet | Dai, Xiao-Yu Zhou, Li Huang, Xiao-Ru Fu, Ping Lan, Hui-Yao |
author_sort | Dai, Xiao-Yu |
collection | PubMed |
description | Chronic Aristolochic Acid Nephropathy (AAN) is a progressive chronic kidney disease related to herb medicine. However, treatment for chronic AAN remains ineffective. We report here that Smad7 is protective and has therapeutic potential for chronic AAN. In a mouse model of chronic AAN, progressive renal injury was associated with a loss of renal Smad7 and disruption of Smad7 largely aggravated the severity of chronic AAN as demonstrated by a significant increase in levels of 24-hour urinary protein excretion, serum creatinine, and progressive renal fibrosis and inflammation. In contrast, restored Smad7 locally in the kidneys of Smad7 knockout mice prevented the progression of chronic AAN. Further studies revealed that worsen chronic AAN in Smad7 knockout mice was associated with enhanced activation of TGF-β/Smad3 and NF-κB signaling pathways, which was reversed when renal Smad7 was restored. Importantly, we also found that overexpression of Smad7 locally in the kidneys with established chronic AAN was capable of attenuating progressive chronic AAN by inactivating TGF-β/Smad3-medated renal fibrosis and NF-κB-driven renal inflammation. In conclusion, Smad7 plays a protective role in the pathogenesis of chronic AAN and overexpression of Smad7 may represent a novel therapeutic potential for chronic AAN. |
format | Online Article Text |
id | pubmed-4494914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44949142015-07-13 Smad7 protects against chronic aristolochic acid nephropathy in mice Dai, Xiao-Yu Zhou, Li Huang, Xiao-Ru Fu, Ping Lan, Hui-Yao Oncotarget Pathology: Research Paper Chronic Aristolochic Acid Nephropathy (AAN) is a progressive chronic kidney disease related to herb medicine. However, treatment for chronic AAN remains ineffective. We report here that Smad7 is protective and has therapeutic potential for chronic AAN. In a mouse model of chronic AAN, progressive renal injury was associated with a loss of renal Smad7 and disruption of Smad7 largely aggravated the severity of chronic AAN as demonstrated by a significant increase in levels of 24-hour urinary protein excretion, serum creatinine, and progressive renal fibrosis and inflammation. In contrast, restored Smad7 locally in the kidneys of Smad7 knockout mice prevented the progression of chronic AAN. Further studies revealed that worsen chronic AAN in Smad7 knockout mice was associated with enhanced activation of TGF-β/Smad3 and NF-κB signaling pathways, which was reversed when renal Smad7 was restored. Importantly, we also found that overexpression of Smad7 locally in the kidneys with established chronic AAN was capable of attenuating progressive chronic AAN by inactivating TGF-β/Smad3-medated renal fibrosis and NF-κB-driven renal inflammation. In conclusion, Smad7 plays a protective role in the pathogenesis of chronic AAN and overexpression of Smad7 may represent a novel therapeutic potential for chronic AAN. Impact Journals LLC 2015-03-30 /pmc/articles/PMC4494914/ /pubmed/25883225 Text en Copyright: © 2015 Dai et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Pathology: Research Paper Dai, Xiao-Yu Zhou, Li Huang, Xiao-Ru Fu, Ping Lan, Hui-Yao Smad7 protects against chronic aristolochic acid nephropathy in mice |
title | Smad7 protects against chronic aristolochic acid nephropathy in mice |
title_full | Smad7 protects against chronic aristolochic acid nephropathy in mice |
title_fullStr | Smad7 protects against chronic aristolochic acid nephropathy in mice |
title_full_unstemmed | Smad7 protects against chronic aristolochic acid nephropathy in mice |
title_short | Smad7 protects against chronic aristolochic acid nephropathy in mice |
title_sort | smad7 protects against chronic aristolochic acid nephropathy in mice |
topic | Pathology: Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494914/ https://www.ncbi.nlm.nih.gov/pubmed/25883225 |
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