Fine-tuning the expression of microRNA-155 controls acetaminophen-induced liver inflammation.
Treatment of acetaminophen (APAP) in overdose can cause a potentially serious and fatal liver injury. MicroRNA-155 (miR-155), a multifunctional microRNA, is known to mediate inflammatory responses via regulating various target genes. In this study, we aimed to study the role of miR-155 in APAP-induced liver injury, using miR-155-/- mice and miR-155 in vivo intervention. We noted that miR-155 expression was significantly increased in liver and blood after APAP treatment. Knockout of miR-155 deteriorated APAP-induced liver damage, with the elevated serum levels of AST and ALT. The levels of various inflammatory mediators, such as TNF-α and IL-6, were markedly augmented in livers in the absence of miR-155. Moreover, miR-155 deficiency aberrantly activated NF-kappa-B signaling via enhancing p65 and IKKε expression. Finally, in vivo administration of miR-155 agomir attenuated APAP-induced liver damage, reduced the serum levels of AST and ALT, and dampened the NF-kB signaling. In conclusion, our data demonstrated that miR-155 protects the mice against APAP-induced liver damage via mediating NF-KB signaling pathway, suggesting that miR-155 might be a potential pharmaceutic target for treatment of APAP-induced liver inflammation.
Department of Vascular Surgery, South Campus, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
Kai
K
Yuan
Department of Vascular Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, China.
Xue
X
Zhang
Department of Vascular Surgery, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
Lei
L
Lv
Department of Vascular Surgery, South Campus, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
Jiwei
J
Zhang
Department of Vascular Surgery, South Campus, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
Wei
W
Liang
Department of Vascular Surgery, South Campus, Ren ji Hospital, School of Medicine, Shanghai Jiao Tong University, China. Electronic address: wangpengrenji@163.com.
Peng
P
Wang
D000082:Acetaminophen / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000082:Acetaminophen
Acetaminophen; Acute liver damage; Inflammation; MicroRNA-155