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Published on: June 3, 2018
C/EBPβ knockdown protects cardiomyocytes from hypertrophy via inhibition of p65-NFκB
1Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu 611130, China.
Insights
CCAAT enhancer-binding protein beta (C/EBPβ) promotes cardiac hypertrophy by activating NFκB signaling. Inhibiting C/EBPβ protects cardiomyocytes, suggesting C/EBPβ as a therapeutic target for cardiac hypertrophy.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Gene Regulation
Background:
- CCAAT enhancer-binding protein beta (C/EBPβ), a transcription factor, is implicated in physiological cardiac hypertrophy.
- The specific role of C/EBPβ in pathological cardiac hypertrophy is not well understood.
Purpose of the Study:
- To investigate the involvement of C/EBPβ in pathological cardiac hypertrophy.
- To elucidate the molecular mechanisms by which C/EBPβ influences cardiac hypertrophy.
Main Methods:
- Assessing C/EBPβ expression in response to hypertrophic stimuli in vitro and in vivo.
- Utilizing C/EBPβ knockdown models to evaluate its effect on phenylephrine (PE)-induced cardiac hypertrophy.
- Examining the impact of C/EBPβ knockdown on p65-NFκB nuclear translocation and DNA binding activity.
Main Results:
- C/EBPβ expression significantly increased under hypertrophic stimulation.
- C/EBPβ knockdown attenuated PE-induced cardiac hypertrophy in cardiomyocytes.
- Knockdown of C/EBPβ reduced the nuclear translocation and DNA binding activity of p65-NFκB.
Conclusions:
- C/EBPβ plays a crucial role in pathological cardiac hypertrophy.
- C/EBPβ inhibition protects cardiomyocytes from hypertrophy, potentially via suppressing NFκB-dependent pathways.
- C/EBPβ emerges as a potential therapeutic target for treating cardiac hypertrophy and C/EBPβ-related cardiomyopathy.
Abstract:
C/EBPβ, a member of the bHLH gene family of DNA-binding transcription factors, has been indicated as a central signal in physiologic hypertrophy. However, the role of C/EBPβ in pathological cardiac hypertrophy remains to be elucidated. In this study, we revealed that C/EBPβ is involved in cardiac hypertrophy, the expression of C/EBPβ were significantly increased in response to hypertrophic stimulation in vitro and in vivo. C/EBPβ knockdown inhibited PE-induced cardiac hypertrophy, and diminished the nuclear translocation and DNA binding activity of p65-NFκB. These results suggested that C/EBPβ knockdown protected cardiomyocytes from hypertrophy, which may be attributed to inhibition of NFκB-dependent transcriptional activity. These findings shed new light on the understanding of C/EBPβ-related cardiomyopathy, and suggest the potential application of C/EBPβ inhibitors in cardiac hypertrophy.
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