title: NF-κB (p65) negatively regulates myocardin-induced cardiomyocyte hypertrophy through multiple mechanisms.
abstract: Myocardin is well known to play a key role in the development of cardiomyocyte hypertrophy. But the exact molecular mechanism regulating myocardin stability and transactivity to affect cardiomyocyte hypertrophy has not been studied clearly. We now report that NF-κB (p65) can inhibit myocardin-induced cardiomyocyte hypertrophy. Then we explore the molecular mechanism of this response. First, we show that p65 can functionally repress myocardin transcriptional activity and also reduce the protein expression of myocardin. Second, the function of myocardin can be regulated by epigenetic modifications. Myocardin sumoylation is known to transactivate cardiac genes, but whether p65 can inhibit SUMO modification of myocardin is still not clear. Our data show that p65 weakens myocardin transcriptional activity through attenuating SUMO modification of myocardin by SUMO1/PIAS1, thereby impairing myocardin-mediated cardiomyocyte hypertrophy. Furthermore, the expression of myocardin can be regulated by several microRNAs, which play important roles in the development and function of the heart and muscle. We next investigated potential role of miR-1 in cardiac hypotrophy. Our results show that p65 can upregulate the level of miR-1 and miR-1 can decrease protein expression of myocardin in cardiac myocytes. Notably, miR-1 expression is also controlled by myocardin, leading to a feedback loop. These data thus provide important and novel insights into the function that p65 inhibits myocardin-mediated cardiomyocyte hypertrophy by downregulating the expression and SUMO modification of myocardin and enhancing the expression of miR-1.
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China; Institute of Biology and Medicine, Wuhan University of Science and Technology, 430000, PR China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Liao
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China. Electronic address: wn929@tust.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
authors.forename: Dong-Wei
authors.initials: DW
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
authors.forename: De-Liang
authors.initials: DL
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Xing
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Institute of Biology and Medicine, Wuhan University of Science and Technology, 430000, PR China.
authors.forename: Dong-Sun
authors.initials: DS
authors.lastname: Cao
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, PR China; Institute of Biology and Medicine, Wuhan University of Science and Technology, 430000, PR China. Electronic address: tony@tust.edu.cn.
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D006984:Hypertrophy / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D025842:SUMO-1 Protein / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D000099251:Myocardin
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D009687:Nuclear Proteins; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; D015534:Trans-Activators; D000099251:Myocardin
keywords: Cardiomyocyte hypertrophy; Myocardin; NF-κB (p65); SUMO modification; miRNAs