MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.
MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.
复制标题
MicroRNA-155 通过 JNK 和 β-arrestin 2 减轻晚期脓毒症引起的心脏功能障碍
DOI：
10.18632/oncotarget.17636
复制
发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Yin D
中科院分区：
文献类型：
--
作者：
Zhou Y;Song Y;Shaikh Z;Li H;Zhang H;Caudle Y;Zheng S;Yan H;Hu D;Stuart C;Yin D
心脏功能障碍与脓毒症的不良预后相关，并导致高死亡风险。在最初的高炎症反应后，大多数患者会进入长期的免疫抑制状态（晚期败血症），从而改变先天免疫和适应性免疫。脓毒症晚期心功能的变化尚不清楚。此前发现 MicroRNA-155 (miR-155) 在免疫激活和心脏功能的调节中发挥重要作用。在本研究中，C57BL/6小鼠经手术发展为脓毒症早期和晚期阶段，并在盲肠结扎穿刺（CLP）后48小时通过尾静脉注射miR-155模拟物。在晚期脓毒症中探讨了 miR-155 对 CLP 诱导的心功能障碍的影响。我们发现，心肌中 miR-155 表达的增加可以预防脓毒症晚期的心功能障碍，这通过减轻脓毒症导致的心输出量减少和增强左心室收缩功能来证明。我们还观察到，miR-155 显着减少巨噬细胞和中性粒细胞向心肌的浸润，并通过抑制 JNK 信号通路减弱炎症反应。此外，β-arrestin 2 (Arrb2) 的过度表达加剧了脓毒症晚期小鼠的死亡率和免疫抑制。此外，转染 miR-155 模拟物可降低 Arrb2 表达，然后恢复晚期脓毒症小鼠的免疫能力并提高生存率。我们的结论是，通过全身施用 miR-155 模拟物来增加 miR-155 表达，可以通过靶向 JNK 相关炎症信号和 Arrb2 介导的免疫抑制来减轻心脏功能障碍并改善晚期脓毒症生存率。
Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.
登录
查看更多内容
DOI：
10.1126/science.aad7993
发表时间：
2016-05-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rialdi A;Campisi L;Zhao N;Lagda AC;Pietzsch C;Ho JSY;Martinez-Gil L;Fenouil R;Chen X;Edwards M;Metreveli G;Jordan S;Peralta Z;Munoz-Fontela C;Bouvier N;Merad M;Jin J;Weirauch M;Heinz S;Benner C;van Bakel H;Basler C;García-Sastre A;Bukreyev A;Marazzi I
通讯作者：
Marazzi I
影响因子：
3.7
作者：
Rouquette-Jazdanian AK;Kortum RL;Li W;Merrill RK;Nguyen PH;Samelson LE;Sommers CL
通讯作者：
Sommers CL
影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
影响因子：
4.8
作者：
Li, Hui;Hu, Dan;Yin, Deling
通讯作者：
Yin, Deling
DOI：
10.1073/pnas.1116125109
发表时间：
2012-05-08
影响因子：
11.1
作者：
Koch, Manuel;Mollenkopf, Hans-Joachim;Meyer, Thomas F.
通讯作者：
Meyer, Thomas F.