MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2
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Yu Zhou1,2, Yan Song3,1, Zahir Shaikh1, Hui Li1, Haiju Zhang1, Yi Caudle1, Shouhua Zheng4, Hui Yan1, Dan Hu2, Charles Stuart1 and Deling Yin1
1Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA
2Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China
3Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
4Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Deling Yin, email: email@example.com
Keywords: microRNA-155, late sepsis, cardiac dysfunction, β-arrestin 2, inflammatory
Received: February 09, 2017 Accepted: April 19, 2017 Published: May 04, 2017
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.
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