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

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.

• Authors: Yu Zhou, Yan Song, Zahir Shaikh, Hui Li, Haiju Zhang, Yi Caudle, Shouhua Zheng, Hui Yan, Dan Hu, Charles Stuart, Deling Yin
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 29 Pg. 47317-47329 (Jul 18 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28525390 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Inflammation Mediators
• MicroRNAs
• Mirn155 microRNA, mouse
• beta-Arrestin 2
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Cytokines (metabolism)
• Disease Models, Animal
• Gene Expression
• Gene Expression Regulation
• Heart Diseases (etiology, metabolism, mortality, physiopathology)
• Heart Function Tests
• Humans
• Inflammation Mediators (metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Macrophages (metabolism)
• Male
• Mice
• MicroRNAs (genetics)
• Myocardium (metabolism)
• Neutrophils (metabolism)
• RNA Interference
• Sepsis (complications, etiology)
• Signal Transduction
• Survival Rate
• Transfection
• beta-Arrestin 2 (metabolism)