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Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice

Hypertension is one of the common causes of pathological cardiac hypertrophy and a major risk for morbidity and mortality of cardiovascular diseases worldwide. Ubiquitin-Specific Protease 7 (USP7), the first identified deubiquitinating enzymes, participated in a variety of biological processes, such...

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Autores principales: Gu, Yu-Hui, Ren, Kai-Wen, Wang, Yu, Wang, Shi-Hao, Yu, Xiao-Hong, Xu, Li-Wen, Li, Hui-Hua, Bi, Hai-Lian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9640964/
https://www.ncbi.nlm.nih.gov/pubmed/36386139
http://dx.doi.org/10.3389/fphar.2022.1021361
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author Gu, Yu-Hui
Ren, Kai-Wen
Wang, Yu
Wang, Shi-Hao
Yu, Xiao-Hong
Xu, Li-Wen
Li, Hui-Hua
Bi, Hai-Lian
author_facet Gu, Yu-Hui
Ren, Kai-Wen
Wang, Yu
Wang, Shi-Hao
Yu, Xiao-Hong
Xu, Li-Wen
Li, Hui-Hua
Bi, Hai-Lian
author_sort Gu, Yu-Hui
collection PubMed
description Hypertension is one of the common causes of pathological cardiac hypertrophy and a major risk for morbidity and mortality of cardiovascular diseases worldwide. Ubiquitin-Specific Protease 7 (USP7), the first identified deubiquitinating enzymes, participated in a variety of biological processes, such as cell proliferation, DNA damage response, tumourigenesis, and apoptosis. However, its role and mechanism in cardiac remodeling remain unclear. Here, our data indicated that USP7 expression was increased during Ang II-induced cardiac hypertrophy and remodeling in mice and humans with heart failure, while the administration of its inhibitor p22077 attenuated cardiac hypertrophy, cardiac fibrosis, inflammation, and oxidase stress. Mechanistically, the administration of p22077 inhibited the multiple signaling pathways, including AKT/ERK, TGF-β/SMAD2/Collagen I/Collagen III, NF-κB/NLRP3, and NAPDH oxidases (NOX2 and NOX4). Taken together, these findings demonstrate that USP7 may be a new therapeutic target for hypertrophic remodeling and HF.
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spelling pubmed-96409642022-11-15 Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice Gu, Yu-Hui Ren, Kai-Wen Wang, Yu Wang, Shi-Hao Yu, Xiao-Hong Xu, Li-Wen Li, Hui-Hua Bi, Hai-Lian Front Pharmacol Pharmacology Hypertension is one of the common causes of pathological cardiac hypertrophy and a major risk for morbidity and mortality of cardiovascular diseases worldwide. Ubiquitin-Specific Protease 7 (USP7), the first identified deubiquitinating enzymes, participated in a variety of biological processes, such as cell proliferation, DNA damage response, tumourigenesis, and apoptosis. However, its role and mechanism in cardiac remodeling remain unclear. Here, our data indicated that USP7 expression was increased during Ang II-induced cardiac hypertrophy and remodeling in mice and humans with heart failure, while the administration of its inhibitor p22077 attenuated cardiac hypertrophy, cardiac fibrosis, inflammation, and oxidase stress. Mechanistically, the administration of p22077 inhibited the multiple signaling pathways, including AKT/ERK, TGF-β/SMAD2/Collagen I/Collagen III, NF-κB/NLRP3, and NAPDH oxidases (NOX2 and NOX4). Taken together, these findings demonstrate that USP7 may be a new therapeutic target for hypertrophic remodeling and HF. Frontiers Media S.A. 2022-10-25 /pmc/articles/PMC9640964/ /pubmed/36386139 http://dx.doi.org/10.3389/fphar.2022.1021361 Text en Copyright © 2022 Gu, Ren, Wang, Wang, Yu, Xu, Li and Bi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Gu, Yu-Hui
Ren, Kai-Wen
Wang, Yu
Wang, Shi-Hao
Yu, Xiao-Hong
Xu, Li-Wen
Li, Hui-Hua
Bi, Hai-Lian
Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice
title Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice
title_full Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice
title_fullStr Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice
title_full_unstemmed Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice
title_short Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice
title_sort administration of usp7 inhibitor p22077 inhibited cardiac hypertrophy and remodeling in ang ii-induced hypertensive mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9640964/
https://www.ncbi.nlm.nih.gov/pubmed/36386139
http://dx.doi.org/10.3389/fphar.2022.1021361
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