MiR-223/Pknox1 axis protects mice from CVB3-induced viral myocarditis by modulating macrophage polarization

Journal Article · Tue May 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.03.004· OSTI ID:23082399

Gou, Weihui; Zhang, Zhen; Yang, Chunfeng; Li, Yumei ^[1]

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1. PICU, First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun, Jilin, 130021 (China)

Highlights: • MiR-223 expression was reduced in CVB3-induced VM. • MiR-223 overexpression alleviated CVB3-induced inflammation and myocarditis. • MiR-223 overexpression inhibited M1 but enhanced M2 macrophage polarization. • MiR-223 directly targeted Pknox1. • Pknox1 overexpression reversed the effects of miR-223 on macrophage polarization. Macrophage polarization plays a crucial role in regulating myocardial inflammation and injuries of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). It has been reported that miR-223 is a potent regulator of inflammatory responses that involved in macrophage polarization. However, the functional roles of miR-223 in CVB3-induced VM still remain unknown. Here, we found that miR-223 expression was significantly down-regulated in heart tissues and heart-infiltrating macrophages of CVB3-infected mice. Up-regulation of miR-223 in vivo protected the mice against CVB3-induced myocardial injuries characterized by the increased body weight and survival, enhanced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), relieved inflammation, depressed creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and aspartate transaminase (AST) levels, reduced production of interferon (IFN)-γ, interleukin (IL)− 6 as well as increased IL-10. We subsequently found that miR-233 up-regulation significantly suppressed the expression of M1 markers (iNOS, TNF-α and CD 86), and promoted the expression of M2 markers (Arginase-1, Fizz-1 and CD 206) in vivo and in vitro. Furthermore, we confirmed that miR-223 directly targeted Pknox1 to inhibit its expression, and the expression of Pknox1 was inversely correlated with miR-223 expression in heart tissues and heart-infiltrating macrophages of CVB3-infected mice. Gain-of-function analyses indicated that Pknox1 overexpression partially reversed the polarization phenotypes regulated by miR-223 overexpression. Taken together, the data suggest that miR-223 protects against CVB3-induced inflammation and myocardial damage, which may partly attribute to the regulation of macrophage polarization via targeting Pknox1.

• OSTI ID: 23082399
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 366; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINOTRANSFERASES
ARGINASE
CREATINE
HEART
INTERFERON
LACTATE DEHYDROGENASE
MACROPHAGES
MICE