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Bcl6 Suppresses Cardiac Fibroblast Activation and Function via Directly Binding to Smad4

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Summary

Bcl6, a critical pro-oncogene of human B-cell lymphomas, can promote tumor progress. Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes. However, the effect of Bcl6 on cardiac fibroblasts is still unclear. The aim of this study was to elucidate the functional role of Bcl6 in cardiac fibroblast activation and function. The neonatal rat cardiac fibroblasts were isolated and cultured. First, transforming growth factor ß1 (TGFß1) was used to stimulate fibroblast activation. A decreased expression level of Bcl6 was observed in fibroblasts after stimulation with TGFß1. Then, cells were transfected with adenovirus Bcl6 to overexpress Bcl6. The results showed that Bcl6 overexpression induced decreased proliferation and reduced activation of fibroblasts which were stimulated with TGFß1. It was found that activated smad2 and smad3 were not changed by overexpressing Bcl6, but smad4 was decreased. Furthermore, co-immunoprecipitation results showed that Bcl6 directly bound to smad4, and induced down-regulation of smad4. At last, smad4 activator could counteract the anti-fibroblast effects of Bcl6. In conclusion, Bcl6 may negatively regulate cardiac fibroblast activation and function by directly binding to smad4.

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Author notes

  1. The authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Jian Ni, Qing-qing Wu, Hai-han Liao, Di Fan & Qi-zhu Tang

  2. Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China

    Jian Ni, Qing-qing Wu, Hai-han Liao, Di Fan & Qi-zhu Tang

  3. Hubei Key Laboratory of Cardiology, Wuhan, 430060, China

    Jian Ni, Qing-qing Wu, Hai-han Liao, Di Fan & Qi-zhu Tang

Authors
  1. Jian Ni
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  2. Qing-qing Wu
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  3. Hai-han Liao
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  4. Di Fan
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  5. Qi-zhu Tang
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Correspondence to Qi-zhu Tang.

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The authors declare that they have no competing financial interests.

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Ni, J., Wu, Qq., Liao, Hh. et al. Bcl6 Suppresses Cardiac Fibroblast Activation and Function via Directly Binding to Smad4. CURR MED SCI 39, 534–540 (2019). https://doi.org/10.1007/s11596-019-2070-y

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  • DOI: https://doi.org/10.1007/s11596-019-2070-y

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