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p53 activates miR-192-5p to mediate vancomycin induced AKI

Pathogenic role of p53 in AKI remains controversial and the underlying mechanism is unclear. Here, we tested whether the inhibition of p53 may ameliorate vancomycin (VAN) induced acute kidney injury (AKI). Mice with p53 knock out (p53-KO) were resistant to VAN induced AKI, indicated by the analysis...

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Autores principales: Chen, Jinwen, Wang, Juan, Li, Huiling, Wang, Shixuan, Xiang, Xudong, Zhang, Dongshan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5150818/
https://www.ncbi.nlm.nih.gov/pubmed/27941921
http://dx.doi.org/10.1038/srep38868
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author Chen, Jinwen
Wang, Juan
Li, Huiling
Wang, Shixuan
Xiang, Xudong
Zhang, Dongshan
author_facet Chen, Jinwen
Wang, Juan
Li, Huiling
Wang, Shixuan
Xiang, Xudong
Zhang, Dongshan
author_sort Chen, Jinwen
collection PubMed
description Pathogenic role of p53 in AKI remains controversial and the underlying mechanism is unclear. Here, we tested whether the inhibition of p53 may ameliorate vancomycin (VAN) induced acute kidney injury (AKI). Mice with p53 knock out (p53-KO) were resistant to VAN induced AKI, indicated by the analysis of renal function, histology, and apoptosis. Mechanistically, AKI was associated with the upregulation of several known p53 target genes, including Bax and p21, and this association was attenuated in p53-KO mice. Furthermore, the expression of miR-192-5p was significantly decreased in the p53-KO kidney tissues. In human renal tubular epithelial cell line (HK-2), VAN induced p53 accumulation and miR-192-5p expression. Both apoptosis of HK-2 cells and expression of miR-192-5p were also suppressed by pifithrin-α. Anti-miR-192-5p significantly blocked VAN-induced apoptosis and caspase activity in HK-2 cells. Consistently, in vivo inhibition of miR-192-5p also suppressed VAN induced AKI. Thus, we provided clinical and genetic evidence that p53 was associated with the development of VAN induced AKI through upregulation of miR-192-5p.
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spelling pubmed-51508182016-12-19 p53 activates miR-192-5p to mediate vancomycin induced AKI Chen, Jinwen Wang, Juan Li, Huiling Wang, Shixuan Xiang, Xudong Zhang, Dongshan Sci Rep Article Pathogenic role of p53 in AKI remains controversial and the underlying mechanism is unclear. Here, we tested whether the inhibition of p53 may ameliorate vancomycin (VAN) induced acute kidney injury (AKI). Mice with p53 knock out (p53-KO) were resistant to VAN induced AKI, indicated by the analysis of renal function, histology, and apoptosis. Mechanistically, AKI was associated with the upregulation of several known p53 target genes, including Bax and p21, and this association was attenuated in p53-KO mice. Furthermore, the expression of miR-192-5p was significantly decreased in the p53-KO kidney tissues. In human renal tubular epithelial cell line (HK-2), VAN induced p53 accumulation and miR-192-5p expression. Both apoptosis of HK-2 cells and expression of miR-192-5p were also suppressed by pifithrin-α. Anti-miR-192-5p significantly blocked VAN-induced apoptosis and caspase activity in HK-2 cells. Consistently, in vivo inhibition of miR-192-5p also suppressed VAN induced AKI. Thus, we provided clinical and genetic evidence that p53 was associated with the development of VAN induced AKI through upregulation of miR-192-5p. Nature Publishing Group 2016-12-12 /pmc/articles/PMC5150818/ /pubmed/27941921 http://dx.doi.org/10.1038/srep38868 Text en Copyright © 2016, The Author(s) 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
Chen, Jinwen
Wang, Juan
Li, Huiling
Wang, Shixuan
Xiang, Xudong
Zhang, Dongshan
p53 activates miR-192-5p to mediate vancomycin induced AKI
title p53 activates miR-192-5p to mediate vancomycin induced AKI
title_full p53 activates miR-192-5p to mediate vancomycin induced AKI
title_fullStr p53 activates miR-192-5p to mediate vancomycin induced AKI
title_full_unstemmed p53 activates miR-192-5p to mediate vancomycin induced AKI
title_short p53 activates miR-192-5p to mediate vancomycin induced AKI
title_sort p53 activates mir-192-5p to mediate vancomycin induced aki
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5150818/
https://www.ncbi.nlm.nih.gov/pubmed/27941921
http://dx.doi.org/10.1038/srep38868
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