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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1021361/full |
| _version_ | 1797985752812879872 |
|---|---|
| author | Yu-Hui Gu Kai-Wen Ren Yu Wang Shi-Hao Wang Xiao-Hong Yu Li-Wen Xu Hui-Hua Li Hai-Lian Bi |
| author_facet | Yu-Hui Gu Kai-Wen Ren Yu Wang Shi-Hao Wang Xiao-Hong Yu Li-Wen Xu Hui-Hua Li Hai-Lian Bi |
| author_sort | Yu-Hui Gu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T07:23:02Z |
| format | Article |
| id | doaj.art-44800c62a3294cdcad0578637e08280a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T07:23:02Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-44800c62a3294cdcad0578637e08280a2022-12-22T04:37:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10213611021361Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive miceYu-Hui Gu0Kai-Wen Ren1Yu Wang2Shi-Hao Wang3Xiao-Hong Yu4Li-Wen Xu5Hui-Hua Li6Hai-Lian Bi7Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Obstetrics, Dalian Maternal and Child Health Institute, Dalian, ChinaDepartment of Emergency Medicine, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing Chaoyang Hospital, Capital Medical University, Beijing, ChinaInstitute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaHypertension 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.1021361/fullcardiac remodelingUSP7 inhibitorP22077inflammationoxidase stress |
| spellingShingle | Yu-Hui Gu Kai-Wen Ren Yu Wang Shi-Hao Wang Xiao-Hong Yu Li-Wen Xu Hui-Hua Li Hai-Lian Bi Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice Frontiers in Pharmacology cardiac remodeling USP7 inhibitor P22077 inflammation oxidase stress |
| 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 | cardiac remodeling USP7 inhibitor P22077 inflammation oxidase stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1021361/full |
| work_keys_str_mv | AT yuhuigu administrationofusp7inhibitorp22077inhibitedcardiachypertrophyandremodelinginangiiinducedhypertensivemice AT kaiwenren administrationofusp7inhibitorp22077inhibitedcardiachypertrophyandremodelinginangiiinducedhypertensivemice AT yuwang administrationofusp7inhibitorp22077inhibitedcardiachypertrophyandremodelinginangiiinducedhypertensivemice AT shihaowang administrationofusp7inhibitorp22077inhibitedcardiachypertrophyandremodelinginangiiinducedhypertensivemice AT xiaohongyu administrationofusp7inhibitorp22077inhibitedcardiachypertrophyandremodelinginangiiinducedhypertensivemice AT liwenxu administrationofusp7inhibitorp22077inhibitedcardiachypertrophyandremodelinginangiiinducedhypertensivemice AT huihuali administrationofusp7inhibitorp22077inhibitedcardiachypertrophyandremodelinginangiiinducedhypertensivemice AT hailianbi administrationofusp7inhibitorp22077inhibitedcardiachypertrophyandremodelinginangiiinducedhypertensivemice |