PMID- 35352799 OWN - NLM STAT- MEDLINE DCOM- 20230322 LR - 20230323 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 119 IP - 1 DP - 2023 Mar 17 TI - RNF207 exacerbates pathological cardiac hypertrophy via post-translational modification of TAB1. PG - 183-194 LID - 10.1093/cvr/cvac039 [doi] AB - AIMS: The heart undergoes pathological remodelling, featured by the hypertrophic growth of cardiomyocytes and increased cardiac fibrosis, under biomechanical stress such as haemodynamic overload. Ring Finger Protein 207 (RNF207) is an E3 ubiquitin ligase that is predominantly expressed in the heart, but its function remains elusive. In this study, we aimed to explore the role of RNF207 in the development of pathological cardiac hypertrophy and dysfunction. METHODS AND RESULTS: Transverse aortic constriction (TAC) surgery was performed on mice to induce cardiac hypertrophy. Cardiac function and remodelling were evaluated by echocardiography, histological assessment, and molecular analyses. Our data indicated that RNF207 overexpression (OE) exacerbated cardiac hypertrophy, fibrosis, and systolic dysfunction. In contrast, TAC-induced cardiac remodelling was profoundly blunted in RNF207 knockdown (KD) hearts. In line with the in vivo findings, RNF207 OE augmented, whereas RNF207 KD alleviated, phenylephrine-induced cardiomyocyte hypertrophy in vitro. Mechanistically, we demonstrated that RNF207 elicited detrimental effects by promoting K63-linked ubiquitination of TAK1-binding protein 1 (TAB1), which triggered the autophosphorylation of transforming growth factor-beta activated kinase 1 (TAK1) and the activation of downstream p38 and c-Jun N-terminal kinase (JNK)1/2 signalling pathways. In the TAB1-KD cardiomyocytes, RNF207-OE-induced cell hypertrophy was significantly attenuated, indicating that RNF207-induced hypertrophy is, at least in part, TAB1-dependent. CONCLUSIONS: This study demonstrates that RNF207 exacerbates pressure overload-induced cardiac hypertrophy and dysfunction via post-translational modification of TAB1. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Yuan, Lin AU - Yuan L AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. AD - Department of Cardiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China. AD - NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, Guangdong, China. FAU - Bu, Shichen AU - Bu S AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Du, Meng AU - Du M AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Wang, Yilong AU - Wang Y AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Ju, Chenhui AU - Ju C AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Huang, Dandan AU - Huang D AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Xu, Wenjing AU - Xu W AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Tan, Xin AU - Tan X AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Liang, Minglu AU - Liang M AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Deng, Shan AU - Deng S AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Yang, Liu AU - Yang L AUID- ORCID: 0000-0002-0972-8511 AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Huang, Kai AU - Huang K AD - Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan 430022, Hubei, China. AD - Clinic Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. AD - Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Huazhong University of Science and Technology, Wuhan, Hubei, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - 0 (Tab1 protein, mouse) SB - IM MH - Animals MH - Mice MH - *Aortic Valve Stenosis/metabolism MH - Cardiomegaly/metabolism MH - Cells, Cultured MH - Disease Models, Animal MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Myocytes, Cardiac/metabolism MH - *Signal Transduction MH - Ubiquitination MH - Ubiquitin-Protein Ligases/metabolism OTO - NOTNLM OT - Cardiac hypertrophy OT - Cell signalling OT - Heart failure COIS- Conflict of interest : none declared. EDAT- 2022/03/31 06:00 MHDA- 2023/03/22 06:00 CRDT- 2022/03/30 08:41 PHST- 2019/11/12 00:00 [received] PHST- 2022/02/14 00:00 [revised] PHST- 2022/03/14 00:00 [accepted] PHST- 2022/03/31 06:00 [pubmed] PHST- 2023/03/22 06:00 [medline] PHST- 2022/03/30 08:41 [entrez] AID - 6555930 [pii] AID - 10.1093/cvr/cvac039 [doi] PST - ppublish SO - Cardiovasc Res. 2023 Mar 17;119(1):183-194. doi: 10.1093/cvr/cvac039.