title: C/EBPβ controls exercise-induced cardiac growth and protects against pathological cardiac remodeling.
abstract: The heart has the ability to grow in size in response to exercise, but little is known about the transcriptional mechanisms underlying physiological hypertrophy. Adult cardiomyocytes have also recently been proven to hold the potential for proliferation, a process that could be of great importance for regenerative medicine. Using a unique RT-PCR-based screen against all transcriptional components, we showed that C/EBPβ was downregulated with exercise, whereas the expression of CITED4 was increased. Reduction of C/EBPβ in vitro and in vivo resulted in a phenocopy of endurance exercise with cardiomyocyte hypertrophy and proliferation. This proliferation was mediated, at least in part, by the increased CITED4. Importantly, mice with reduced cardiac C/EBPβ levels displayed substantial resistance to cardiac failure upon pressure overload. These data indicate that C/EBPβ represses cardiomyocyte growth and proliferation in the adult mammalian heart and that reduction in C/EBPβ is a central signal in physiologic hypertrophy and proliferation.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, MA 02115, USA.
authors.forename: Pontus
authors.initials: P
authors.lastname: Boström
authors.forename: Nina
authors.initials: N
authors.lastname: Mann
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Quintero
authors.forename: Eva R
authors.initials: ER
authors.lastname: Plovie
authors.forename: Daniela
authors.initials: D
authors.lastname: Panáková
authors.forename: Rana K
authors.initials: RK
authors.lastname: Gupta
authors.forename: Chunyang
authors.initials: C
authors.lastname: Xiao
authors.forename: Calum A
authors.initials: CA
authors.lastname: MacRae
authors.forename: Anthony
authors.initials: A
authors.lastname: Rosenzweig
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; C545014:Cebpb protein, rat; C499189:Cited4 protein, mouse; D014157:Transcription Factors