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  • Title: MiR-155 aggravated septic liver injury by oxidative stress-mediated ER stress and mitochondrial dysfunction via targeting Nrf-2.
    Author: Yang ZB, Chen WW, Chen HP, Cai SX, Lin JD, Qiu LZ.
    Journal: Exp Mol Pathol; 2018 Dec; 105(3):387-394. PubMed ID: 30218645.
    Abstract:
    OBJECTIVE: Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is confirmed to play crucial roles in septic liver injury. The present study aims to investigate the mechanisms of miR-155 in septic liver injury. METHODS: The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) in mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+ miR-155 antagomir. The survival rate and body weight were monitored. Liver injury was assessed by H&E staining. The levels of serum ALT and inflammatory cytokines were determined by ELISA kits. Oxidative stress was detected by MDA and SOD detection kits. The miR-155, Nrf-2, and markers related to oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial injury and apoptosis were detected by western blotting and qPCR. Apoptosis in liver tissues was detected by TUNELstaining. RESULTS: MiR-155 antagomir alleviated liver injury as evidenced by enhancing survival rate and body weight, inhibiting inflammatory cell infiltration, liver cells necrosis and decreasing ALT level. The productions of TNF-α, IL-6 were suppressed, while anti-inflammatory cytokine IL-10 was promoted by miR-155 antagomir. Oxidative stress was inhibited by miR-155 antagomir via enhancing nuclear factor, erythroid 2-like 2 (Nrf-2) expression. ER stress and Cytochrome C (Cyto-C) release were restrained by miR-155 antagomir. Sepsis-induced apoptosis was repressed by miR-155 antagomir as manifested by the decreased levels of Bax, cleaved caspase-12, 9 and 3, and increased levels of Bcl-2 and uncleaved PARP. CONCLUSION: MiR-155 antagomir relieved septic liver injury through inhibiting oxidative stress-mediated ER stress, mitochondrial dysfunction and apoptosis via targeting Nrf-2, suggesting miR-155 as a therapeutic target for septic liver injury.
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