西亚试剂：C/EBPβ Controls Exercise-Induced Cardiac Growth and Protect

C/EBPβ Controls Exercise-Induced Cardiac Growth and Protects against Pathological Cardiac Remodeling

Authors

Pontus Bostr?m, Nina Mann, Jun Wu, Pablo A. Quintero, Eva R. Plovie, Daniela Panáková, Rana K. Gupta, Chunyang Xiao, Calum A. MacRae, Anthony Rosenzweig, Bruce M. Spiegelman

Highlights

Endurance exercise of mice induces cardiomyocyte proliferation

Endurance exercise causes a reduction of C/EBPβ expression and an increase of CITED4

Reduction of C/EBPβ in vitro induces cellular hypertrophy and proliferation via CITED4

Genetic reduction of C/EBPβ in vivo results in a phenocopy of the exercised heart

Summary

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.