MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2

Yu Zhou, Yan Song, Zahir Shaikh, Hui Li, Haiju Zhang, Yi Caudle, Shouhua Zheng, Hui Yan, Dan Hu, Charles Stuart, Deling Yin

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)47317-47329
Number of pages13
JournalOncotarget
Volume8
Issue number29
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • Cardiac dysfunction
  • Inflammatory
  • Late sepsis
  • MicroRNA-155
  • β-arrestin 2

ASJC Scopus subject areas

  • Oncology

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