miR-146a Attenuates Sepsis-Induced Myocardial Dysfunction by Suppressing IRAK1 and TRAF6 via Targeting ErbB4 Expression.
miR-146a Attenuates Sepsis-Induced Myocardial Dysfunction by Suppressing IRAK1 and TRAF6 via Targeting ErbB4 Expression.
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miR-146a 通过靶向 ErbB4 表达抑制 IRAK1 和 TRAF6 减轻脓毒症引起的心肌功能障碍
DOI：
10.1155/2018/7163057
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发表时间：
2018
影响因子：
--
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
An R;Feng J;Xi C;Xu J;Sun L
心肌功能障碍是脓毒症的主要表现，且与死亡率增加密切相关。微小RNA - 146是被确定为在脂多糖（LPS）诱导的先天免疫和炎症反应中一种重要的负性调节因子的微小RNA之一。我们旨在确定miR - 146a在脓毒症诱导的、伴有ErbB4信号诱导的心脏功能障碍中的作用及其潜在的调节机制。用LPS处理H9C2细胞以诱导脓毒症，miR - 146a过表达显著提高细胞活力，减少细胞凋亡和活性氧（ROS）水平，并减弱包括肿瘤坏死因子 - α（TNF - α）和白细胞介素 - 1β（IL - 1β）在内的促炎细胞因子的释放。通过蛋白质印迹法检测ErbB4、磷酸化核因子 - κB（p - NF - κB）、核因子 - κB（NF - κB）、肿瘤坏死因子受体相关因子6（TRAF6）、白细胞介素 - 1受体相关激酶1（IRAK1）、半胱天冬酶3（caspase 3）、B细胞淋巴瘤 - 2（Bcl - 2）和Bax的水平。miR - 146a过表达显著提高ErbB4表达，降低TRAF6、IRAK1、caspase 3的表达以及NF - κB的磷酸化水平，并且还提高Bcl - 2 / Bax比值，表明对炎症和细胞凋亡的抑制。使用siErbB4后，所有的保护作用均消失。总之，我们的结果表明，在LPS诱导的脓毒症中，miR - 146a过表达通过靶向ErbB4对核因子 - κB激活和炎症细胞因子产生负性调节，从而减轻心肌损伤。
Myocardial dysfunction is a major manifestation of sepsis and closely associated with the increased mortality. MicroRNA-146 is one of the most important microRNAs identified as a potent negative regulator in innate immune and inflammatory responses induced by lipopolysaccharide (LPS). We aimed to identify the role and potential regulatory mechanism of miR-146a in sepsis-induced cardiac dysfunction with the induction of ErbB4 signaling. H9C2 cells were treated with LPS to induce sepsis, and miR-146a overexpression significantly increased the cell viability, reduced the apoptosis and ROS level, and attenuated the release of proinflammatory cytokines including TNF-α and IL-1β. Levels of ErbB4, p-NF-κB, NF-κB, TRAF6, IRAK1, caspase 3, Bcl-2, and Bax were measured by Western blot. The overexpression of miR-146a significantly increased the ErbB4 expression, decreased the expression of TRAF6, IRAK1, caspase 3, and the phosphorylation level of NF-κB, and also increased the Bcl-2/Bax ratio, suggesting the inhibition of inflammation and apoptosis. The protective effects were all abolished by the use of siErbB4. In conclusion, our results demonstrated that the overexpression of miR-146a mitigates myocardial injury by negatively regulating NF-κB activation and inflammatory cytokine production via targeting ErbB4 in LPS-induced sepsis.
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影响因子：
168.9
作者：
Sharshar, T;Gray, F;Annane, D
通讯作者：
Annane, D
影响因子：
3.7
作者：
Antonucci, Elio;Fiaccadori, Enrico;Scolletta, Sabino
通讯作者：
Scolletta, Sabino
影响因子：
9.6
作者：
VINCENT, JL;BAKKER, J;DUPONT, E
通讯作者：
DUPONT, E
DOI：
10.1152/ajpheart.0655.2001
发表时间：
2003-08-01
影响因子：
4.8
作者：
Thomas, JA;Haudek, SB;Giroir, BP
通讯作者：
Giroir, BP
miR-146a对于脂多糖（LPS）诱导的小鼠肾脏缺血/再灌注损伤的交叉耐受至关重要
影响因子：
4.6
作者：
Dai, Yan;Jia, Ping;Ding, Xiaoqiang
通讯作者：
Ding, Xiaoqiang