EMBO Molecular Medicine (Nov 2019)
Nuclear receptor corepressor 1 represses cardiac hypertrophy
- Chao Li,
- Xue‐Nan Sun,
- Bo‐Yan Chen,
- Meng‐Ru Zeng,
- Lin‐Juan Du,
- Ting Liu,
- Hui‐Hui Gu,
- Yuan Liu,
- Yu‐Lin Li,
- Lu‐Jun Zhou,
- Xiao‐Jun Zheng,
- Yu‐Yao Zhang,
- Wu‐Chang Zhang,
- Yan Liu,
- Chaoji Shi,
- Shuai Shao,
- Xue‐Rui Shi,
- Yi Yi,
- Xu Liu,
- Jun Wang,
- Johan Auwerx,
- Zhao V Wang,
- Feng Jia,
- Ruo‐Gu Li,
- Sheng‐Zhong Duan
Affiliations
- Chao Li
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Xue‐Nan Sun
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Bo‐Yan Chen
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Meng‐Ru Zeng
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Lin‐Juan Du
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Ting Liu
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Hui‐Hui Gu
- Shanghai Jing'an District Central Hospital Fudan University Shanghai China
- Yuan Liu
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Yu‐Lin Li
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Lu‐Jun Zhou
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Xiao‐Jun Zheng
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Yu‐Yao Zhang
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Wu‐Chang Zhang
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Yan Liu
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Chaoji Shi
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- Shuai Shao
- Department of Neurosurgery Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
- Xue‐Rui Shi
- Department of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University Shanghai China
- Yi Yi
- Department of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University Shanghai China
- Xu Liu
- Department of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University Shanghai China
- Jun Wang
- Shanghai Jing'an District Central Hospital Fudan University Shanghai China
- Johan Auwerx
- Laboratory of Integrative and Systems Physiology Institute of Bioengineering École Polytechnique Fédérale de Lausanne (EPFL) Lausanne Switzerland
- Zhao V Wang
- Division of Cardiology Department of Internal Medicine University of Texas Southwestern Medical Center Dallas TX USA
- Feng Jia
- Department of Neurosurgery Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai China
- Ruo‐Gu Li
- Department of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University Shanghai China
- Sheng‐Zhong Duan
- Laboratory of Oral Microbiota and Systemic Diseases Shanghai Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
- DOI
- https://doi.org/10.15252/emmm.201809127
- Journal volume & issue
-
Vol. 11,
no. 11
pp. n/a – n/a
Abstract
Abstract The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte‐specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at baseline and had more severe cardiac hypertrophy and dysfunction after pressure overload. Knockdown of NCoR1 exacerbated whereas overexpression mitigated phenylephrine‐induced cardiomyocyte hypertrophy. Mechanistic studies revealed that myocyte enhancer factor 2a (MEF2a) and MEF2d mediated the effects of NCoR1 on cardiomyocyte hypertrophy. The receptor interaction domains (RIDs) of NCoR1 interacted with MEF2a to repress its transcriptional activity. Furthermore, NCoR1 formed a complex with MEF2a and class IIa histone deacetylases (HDACs) to suppress hypertrophy‐related genes. Finally, overexpression of RIDs of NCoR1 in the heart attenuated cardiac hypertrophy and dysfunction induced by pressure overload. In conclusion, NCoR1 cooperates with MEF2 and HDACs to repress cardiac hypertrophy. Targeting NCoR1 and the MEF2/HDACs complex may be an attractive therapeutic strategy to tackle pathological cardiac hypertrophy.
Keywords
