C/EBPbeta controls exercise-induced cardiac growth and protects against pathological cardiac remodeling (Cell, 2010, 143:1072-1083)

報告日期: 2011/04/26
報告時間: 15:10/16:00
報告學生: 陳宛君 (英文報告)
講評老師: 莫凡毅

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0426-1.pdf

C/EBPb Controls Exercise-Induced Cardiac Growth and Protects against
Pathological Cardiac Remodeling
Cell. 2010; 143(7):1072-83
Speaker: Wan-Chun Chen
Commentator: Dr. Fan-E, Mo
Date: 2011/04/22 (pm 15:10-16:00)
Background: Physiological or pathophysiological stimuli, such as exercise or hypertension, respectively, have been reported to regulate pressure and/or volume changes of heart. Numerous studies have reported the role of transcription factors in pathological hypertrophy1, but the molecular mechanisms controlling physiological hypertrophy is rarely documented. CCAAT/enhancer-binding protein beta (C/EBPb), a member of the bHLH gene family of DNA binding transcription factor, is involved in the regulation of cell proliferation and differentiation in many tissues, including adipose tissue and liver2. However, the role of C/EBPb in the regulation of cardiomyocytes is not fully understood.
Objective: To investigate the transcriptional mechanisms underlying physiological hypertrophy and access the role of C/EBPb in cardiomyocytes.
Results: The authors created an endurance exercise murine model to study the physiological hypertrophy and proliferation in cardiomyocytes. By using a unique RT-PCR-based screening, the authors found that endurance exercise resulted in the downregulation of C/EBPb, while the proproliferativeCITED4 is increased. Inhibition of C/EBPβ by siRNA induced hypertrophy and proliferation in cultured cardiomyocytes, consistent with the finding in the in vivo model. To explore the molecular mechanisms, the authors demonstrated that inhibition of C/EBPb dramatically increased SRF binding to the promoters of two differentiation-related genes, a-MHC and Gata4, in cardiomyocyte. Furthermore, C/EBPb-controlled cardiomyocyte proliferation was observed in the zebrafish embryo as well. More importantly, the heart function in C/EBPb heterozygous mice is found to be improved upon pressure overload-induced cardiac failure.
Conclusion: Endurance exercise-induced inhibition of C/EBPb results in the induction of cardiac-specific genes both in vitro and in vivo to against the pressure overload-induced pathological changes.
1.    H. Akazawa and I. Komuro, Roles of cardiac transcription factors in cardiac hypertrophy, Circ. Res. 92 (2003), pp. 1079–1088.
2.    T. Sebastian and P.F. Johnson, Stop and go: anti-proliferative and mitogenic functions of the transcription factor C/EBPb, Cell Cycle 5 (2006), pp. 953–957.