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Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury

BACKGROUND: Angiotensin II (Ang II) contributes to the progression of glomerulosclerosis, mainly by inducing podocyte injury. Convincing evidence indicates that the mTOR inhibitor rapamycin could play a fundamental role in protection against podocyte injury. Nestin, a major cytoskeletal protein, is...

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Autores principales: Shi, Huimin, Zhao, Yajie, He, Tiantian, Wen, Xianli, Qu, Gaoting, Li, Shanwen, Gan, Weihua, Zhang, Aiqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863685/
https://www.ncbi.nlm.nih.gov/pubmed/35149934
http://dx.doi.org/10.1007/s11033-021-07029-x
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author Shi, Huimin
Zhao, Yajie
He, Tiantian
Wen, Xianli
Qu, Gaoting
Li, Shanwen
Gan, Weihua
Zhang, Aiqing
author_facet Shi, Huimin
Zhao, Yajie
He, Tiantian
Wen, Xianli
Qu, Gaoting
Li, Shanwen
Gan, Weihua
Zhang, Aiqing
author_sort Shi, Huimin
collection PubMed
description BACKGROUND: Angiotensin II (Ang II) contributes to the progression of glomerulosclerosis, mainly by inducing podocyte injury. Convincing evidence indicates that the mTOR inhibitor rapamycin could play a fundamental role in protection against podocyte injury. Nestin, a major cytoskeletal protein, is stably expressed in podocytes and correlates with podocyte damage. The purpose of this study was to investigate the effect of rapamycin on podocyte injury induced by Ang II and to clarify the role and mechanism of nestin in the protective effect of rapamycin of podocyte injury. METHODS AND RESULTS: We established an Ang II perfusion animal model, and the effects of rapamycin treatment on podocytes were investigated in vivo. In vitro, podocytes were stimulated with Ang II and rapamycin to observe podocyte injury, and nestin-siRNA was transfected to investigate the underlying mechanisms. We observed that Ang II induced podocyte injury both in vivo and in vitro, whereas rapamycin treatment relieved Ang II-induced podocyte injury. We further found that nestin co-localized with p-mTOR in glomeruli, and the protective effect of rapamycin was reduced by nestin-siRNA in podocytes. Moreover, co-IP indicated the interaction between nestin and p-mTOR, and nestin could affect podocyte injury via the mTOR/P70S6K signaling pathway. CONCLUSION: We demonstrated that rapamycin attenuated podocyte apoptosis via upregulation of nestin expression through the mTOR/P70S6K signaling pathway in an Ang II-induced podocyte injury.
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spelling pubmed-88636852022-03-02 Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury Shi, Huimin Zhao, Yajie He, Tiantian Wen, Xianli Qu, Gaoting Li, Shanwen Gan, Weihua Zhang, Aiqing Mol Biol Rep Original Article BACKGROUND: Angiotensin II (Ang II) contributes to the progression of glomerulosclerosis, mainly by inducing podocyte injury. Convincing evidence indicates that the mTOR inhibitor rapamycin could play a fundamental role in protection against podocyte injury. Nestin, a major cytoskeletal protein, is stably expressed in podocytes and correlates with podocyte damage. The purpose of this study was to investigate the effect of rapamycin on podocyte injury induced by Ang II and to clarify the role and mechanism of nestin in the protective effect of rapamycin of podocyte injury. METHODS AND RESULTS: We established an Ang II perfusion animal model, and the effects of rapamycin treatment on podocytes were investigated in vivo. In vitro, podocytes were stimulated with Ang II and rapamycin to observe podocyte injury, and nestin-siRNA was transfected to investigate the underlying mechanisms. We observed that Ang II induced podocyte injury both in vivo and in vitro, whereas rapamycin treatment relieved Ang II-induced podocyte injury. We further found that nestin co-localized with p-mTOR in glomeruli, and the protective effect of rapamycin was reduced by nestin-siRNA in podocytes. Moreover, co-IP indicated the interaction between nestin and p-mTOR, and nestin could affect podocyte injury via the mTOR/P70S6K signaling pathway. CONCLUSION: We demonstrated that rapamycin attenuated podocyte apoptosis via upregulation of nestin expression through the mTOR/P70S6K signaling pathway in an Ang II-induced podocyte injury. Springer Netherlands 2022-02-11 2022 /pmc/articles/PMC8863685/ /pubmed/35149934 http://dx.doi.org/10.1007/s11033-021-07029-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Shi, Huimin
Zhao, Yajie
He, Tiantian
Wen, Xianli
Qu, Gaoting
Li, Shanwen
Gan, Weihua
Zhang, Aiqing
Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury
title Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury
title_full Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury
title_fullStr Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury
title_full_unstemmed Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury
title_short Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury
title_sort rapamycin attenuated podocyte apoptosis via upregulation of nestin in ang ii-induced podocyte injury
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863685/
https://www.ncbi.nlm.nih.gov/pubmed/35149934
http://dx.doi.org/10.1007/s11033-021-07029-x
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