Silibinin Attenuates Cardiac Hypertrophy and Fibrosis Through Blocking EGFR-Dependent Signaling
Silibinin Attenuates Cardiac Hypertrophy and Fibrosis Through Blocking EGFR-Dependent Signaling
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水飞蓟宾通过阻断 EGFR 依赖性信号传导减轻心脏肥大和纤维化
DOI：
10.1002/jcb.22623
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发表时间：
2010-08-01
影响因子：
4
通讯作者：
Li, Hongliang
中科院分区：
文献类型：
--
作者：
Ai, Wen;Zhang, Yan;Li, Hongliang
心肌肥厚是心衰的主要决定因素，表皮生长因子受体（EGFR）在心肌肥厚中起重要作用。因为水飞蓟宾在体内和体外都能抑制EGFR。我们假设水飞蓟宾可以通过破坏EGFR信号通路来减轻心脏肥厚。在这项研究中，我们用血管紧张素II （Ang II）诱导的新生儿心肌细胞和成纤维细胞和主动脉束带（AB）小鼠模型来验证这一假设。水飞蓟宾能明显阻断压力过载引起的心脏肥厚反应。此外，滑动-朗姆酒显著降低了EGFR的生成。这些有益作用与egfr依赖性ERK 1/2、PI3K/Akt信号级联的衰减有关。我们进一步证明水飞蓟宾通过阻断NF-kappa B和tgf - β 1/Smad信号通路的激活，在体外和体内减少炎症和纤维化。我们的研究结果表明，水飞蓟宾通过阻断EGFR活性和EGFR依赖的不同细胞内信号通路，具有防止心脏肥大、炎症和纤维化的潜力。中国生物医学工程学报，2010(3):389 - 391。公司
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 an model by aortic banding (AB) mice. Our data revealed that silibinin obviously blocked cardiac hypertrophic responses Induced by pressure overload Meanwhile. slid-rum markedly reduced the increased generation of EGFR Moreover. these beneficial effects were associated with attenuation of the EGFR-dependent ERK 1/2, PI3K/Akt signaling cascade. We further demonstrated silibinin decreased inflammation and fibrosis by blocking the activation of NF-kappa B and TGF-beta 1/Smad signaling pathways in vitro and in viva. 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 (C) 2010 Wiley-Liss. Inc