Annals of hepatology · 2020
miRNA-338-3p/CAMK IIα signaling pathway prevents acetaminophen-induced acute liver inflammation in vivo.
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Zhang Chen, Kang Li, Zhu Haihui, Li Jing, Fang Rong
Аннотация
INTRODUCTION AND OBJECTIVES: N-acetyl-p-aminophenol (APAP)-induced liver injury is a major clinical challenge worldwide. The present study investigated the molecular role of microRNA (miR)-338-3p in the development of APAP-induced acute liver injury.
MATERIALS AND METHODS: B6 mice were treated with an miR-338-3p agomir, antagomir, and intraperitoneally injected with APAP 24h later to induce acute liver injury. Histological analysis was performed to evaluate the degree of liver injury. The gene expression of miR-338-3p and its downstream regulators was measured by reverse transcription-quantitative PCR and western blot. The miR target was validated using a luciferase reporter assay.
RESULTS: The results revealed that miR-338-3p was significantly upregulated following the intraperitoneal administration of APAP. Augmenting miR-338-3p alleviated acute liver injury caused by APAP overdose, while silencing of miR-338-3p exhibited a detrimental effect. Moreover, miR-338-3p inhibited the expression of pro-inflammatory cytokines by preventing the aberrant activation of inflammatory signaling pathways, including the nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, calcium/calmodulin-dependent protein kinase IIα (CAMK IIα) was identified as a direct target of miR-338-3p.
CONCLUSION: The present study demonstrated that miR-338-3p inhibited inflammation in APAP-induced acute liver injury.
MATERIALS AND METHODS: B6 mice were treated with an miR-338-3p agomir, antagomir, and intraperitoneally injected with APAP 24h later to induce acute liver injury. Histological analysis was performed to evaluate the degree of liver injury. The gene expression of miR-338-3p and its downstream regulators was measured by reverse transcription-quantitative PCR and western blot. The miR target was validated using a luciferase reporter assay.
RESULTS: The results revealed that miR-338-3p was significantly upregulated following the intraperitoneal administration of APAP. Augmenting miR-338-3p alleviated acute liver injury caused by APAP overdose, while silencing of miR-338-3p exhibited a detrimental effect. Moreover, miR-338-3p inhibited the expression of pro-inflammatory cytokines by preventing the aberrant activation of inflammatory signaling pathways, including the nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, calcium/calmodulin-dependent protein kinase IIα (CAMK IIα) was identified as a direct target of miR-338-3p.
CONCLUSION: The present study demonstrated that miR-338-3p inhibited inflammation in APAP-induced acute liver injury.