Inhibition of microRNA-143-3p attenuates myocardial hypertrophy by inhibiting inflammatory response
Inhibition of microRNA-143-3p attenuates myocardial hypertrophy by inhibiting inflammatory response
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抑制 microRNA-143-3p 可通过抑制炎症反应来减轻心肌肥厚。
DOI：
10.1002/cbin.11053
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发表时间：
2018-11-01
影响因子：
3.9
通讯作者：
Shi, Kaiyao
中科院分区：
文献类型：
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作者：
Yu, Bo;Zhao, Yanan;Shi, Kaiyao
微小RNA - 143 - 3p（miR - 143 - 3p）参与炎症反应的起始以及心血管疾病的进展。心肌肥大是众多心血管疾病中的常见症状。在本项研究中，我们试图通过聚焦miR - 143 - 3p与炎症的关联，来论证其在心肌肥大发展过程中的作用。在体内，通过主动脉弓缩窄（TAC）法诱导心肌肥大；在体外，则通过给予过氧化氢（H₂O₂）诱导。我们检测了动物心脏组织和H9c2细胞中miR - 143 - 3p及其下游效应分子的表达状态。此外，还评估了抑制miR - 143 - 3p对H₂O₂诱导的细胞外调节蛋白激酶5（ERK5）/过氧化物酶体增殖物激活受体（PPAR）/核因子 - κB（NF - κB）轴变化的影响。TAC在大鼠心脏组织中诱导了氧化应激和炎症反应，这与miR - 143 - 3p和磷酸化ERK5（p - ERK5）表达增加相关。然而，miR - 143 - 3p的上调表达对其直接靶标ERK5的表达并无影响。体外实验结果显示，给予H₂O₂会增加miR - 143 - 3p和p - EKR5水平，并诱导NF - κB通路的激活。抑制miR - 143 - 3p后，EKR5和NF - κB通路的激活受到抑制，而PPAR的表达上调。本研究表明，miR - 143 - 3p对心肌肥大诱导的炎症反应起始至关重要。miR - 143 - 3p上调后ERK5的激活似乎是一种补充性反应，以诱导后续的抗炎信号转导，这一点还需进一步探究。
MicroRNA-143-3p (miR-143-3p) is involved in the initiation of inflammatory response and the progression of cardiovascular diseases. Myocardial hypertrophy is a common symptom in numerous cardiovascular diseases. In the current study, we attempted to demonstrate the role of miR-143-3p in the development of myocardial hypertrophy by focusing on its association with inflammation. Myocardial hypertrophy was induced by transverse aortic constriction (TAC) method in vivo and by H2O2 administration in vitro. The expression status of miR-143-3p and downstream effectors were detected in animal heart tissues and H9c2 cells. Furthermore, the effect of miR-143-3p inhibition on H2O2-induced changes in ERK5/PPAR/NF-B axis was assessed. TAC induced oxidative stress and inflammation in rat heart tissues, which was associated with the increased expressions of miR-143-3p and p-ERK5. However, the up-regulated expression of miR-143-3p had no effect on the expression of ERK5, which was a direct target of miR-143-3p. The results of in vitro assays showed that H2O2 administration increased the levels of miR-143-3p and p-EKR5 and induced the activation of NF-B pathway. After the inhibition of miR-143-3p, the activation of EKR5 and NF-B pathway was suppressed, whereas the expression of PPAR was up-regulated. The current study demonstrated that miR-143-3p is crucial to the initiation of inflammatory response induced by myocardial hypertrophy. The activation of ERK5 following miR-143-3p up-regulation appears to be a complementary response to induce the subsequent anti-inflammatory signaling transduction, which needed further exploration.