UBE3A alleviates isoproterenol-induced cardiac hypertrophy through the inhibition of the TLR4/MMP-9 signaling pathway
UBE3A alleviates isoproterenol-induced cardiac hypertrophy through the inhibition of the TLR4/MMP-9 signaling pathway
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UBE3A 通过抑制 TLR4/MMP-9 信号通路减轻异丙肾上腺素诱导的心脏肥大
DOI：
10.1093/abbs/gmz119
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发表时间：
2020-01-01
影响因子：
3.7
通讯作者：
Jin, Yueling
中科院分区：
文献类型：
--
作者：
Li, Yanfei;Ma, Linlin;Jin, Yueling
心肌肥厚被认为是心脏功能相关死亡的主要因素。在本研究中，我们探讨了异丙肾上腺素诱导心肌肥厚的可能机制。结果表明，异丙肾上腺素诱导AC16细胞心肌肥大，表现为细胞表面积增大，肥大标志物增多，并伴有泛素蛋白连接酶E3a(UBE3A)表达增加。此外，被siRNAs敲除的UBE3A促进了心肌肥厚，提示异丙肾上腺素诱导的UBE3A表达增加可能是一种保护性反应，UBE3A可能是一种抗心肌肥厚的保护因子。我们的研究还发现，UBE3A基因敲除增加了TLR4/MMP9通路的蛋白表达，这表明UBE3A介导的保护作用可能与阻断TLR4/MMP9信号通路有关。因此，UBE3A基因可能成为治疗心肌肥厚的潜在靶基因。
Cardiac hypertrophy is considered to be a leading factor in heart function-related deaths. In this study, we explored the potential mechanism underlying cardiac hypertrophy induced by isoproterenol. Our results showed that isoproterenol induced cardiac hypertrophy in AC16 cells, as reflected by the increased cell surface area and increased hypertrophic markers, which was accompanied by increased ubiquitin-protein ligase E3a (UBE3A) expression. Moreover, UBE3A knockdown by siRNAs accelerated cardiac hypertrophy, suggesting that increased UBE3A expression induced by isoproterenol might be a protective response and UBE3A might be a protective factor against cardiac hypertrophy. Our study also revealed that UBE3A knockdown increased the protein expression of the TLR4/MMP-9 pathway that has been shown to be associated with cardiac hypertrophy, which suggested that UBE3A-mediated protection is likely to be associated with the blockade of the TLR4/MMP-9 signaling pathway. UBE3A might be thus a potential target gene for the treatment of cardiac hypertrophy.