Silibinin attenuates cardiac hypertrophy and fibrosis through blocking EGFR‐dependent signaling |
| |
Authors: | Wen Ai Yan Zhang Qi‐Zhu Tang Ling Yan Zhou‐Yan Bian Chen Liu He Huang Xue Bai Lu Yin Hongliang Li |
| |
Institution: | 1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China;2. Cardiovascular Research Institute of Wuhan University, Wuhan 430060, PR China;3. Department of Cardiology, The First Affiliated Hospital, Sun Yat‐Sen University, Guangzhou, China |
| |
Abstract: | Cardiac hypertrophy is a major determinant of heart failure. The epidermal growth factor receptor (EGFR) plays an important role in cardiac hypertrophy. Since silibinin suppresses EGFR in vitro and in vivo, we hypothesized that silibinin would attenuate cardiac hypertrophy through disrupting EGFR signaling. In this study, we examined this hypothesis using neonatal cardiac myocytes and fibroblasts induced by angiotensin II (Ang II) and animal model by aortic banding (AB) mice. Our data revealed that silibinin obviously blocked cardiac hypertrophic responses induced by pressure overload. Meanwhile, silibinin markedly reduced the increased generation of EGFR. Moreover, these beneficial effects were associated with attenuation of the EGFR‐dependent ERK1/2, PI3K/Akt signaling cascade. We further demonstrated silibinin decreased inflammation and fibrosis by blocking the activation of NF‐κB and TGF‐β1/Smad signaling pathways in vitro and in vivo. Our results indicate that silibinin has the potential to protect against cardiac hypertrophy, inflammation, and fibrosis through blocking EGFR activity and EGFR‐dependent different intracellular signaling pathways. J. Cell. Biochem. 110: 1111–1122, 2010. Published 2010 Wiley‐Liss, Inc. |
| |
Keywords: | silibinin cardiac hypertrophy EGFR fibrosis signaling pathway |
|
|