title: Inhibition of microRNA‑155 relieves sepsis‑induced liver injury through inactivating the JAK/STAT pathway.
abstract: The present study aimed to investigate whether the microRNA (miR)‑155 inhibitor has an anti‑inflammatory effect on sepsis‑associated liver injury and whether this effect is associated with the activity of the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. BALB/c mice were randomly divided into three groups (n=40 per group): Control, lipopolysaccharide (LPS) and miR‑155 inhibitor plus LPS groups. Liver injury was induced by injection of LPS (20 mg kg‑1). In the inhibitor plus LPS group, LPS was administered after injecting the miR‑155 inhibitor (80 mg kg‑1) for 3 days. Liver tissues were collected at 6, 12, 24 and 48 h after LPS exposure. Hematoxylin and eosin was used to identify the histological changes in the liver. The expression levels of miR‑155, suppressor of cytokine signaling 1 (SOCS1) and STAT1 were determined by reverse transcription‑quantitative polymerase chain reaction. The protein expression of tumor necrosis factor (TNF)‑α and interleukin (IL)‑10 were detected by ELISA. miR‑155 inhibitor pretreatment alleviated the symptoms of LPS‑exposed mice, and reduced LPS‑induced mortality and liver injury. Compared with the LPS group, expression of miR‑155 was significantly reduced in the miR‑155 inhibitor plus LPS group at 6 h (P<0.05). SOCS1 expression was significantly increased in miR‑155 inhibitor plus LPS group compared with the control and the LPS group at 12 h (P<0.05). There was a lower level of STAT1 in the miR‑155 inhibitor plus LPS group compared with the LPS group (P<0.05). In addition, TNF‑α and IL‑10 were significantly decreased in the miR‑155 inhibitor plus LPS group compared with the LPS group (P<0.05). In conclusion, the miR‑155 inhibitor relieves liver injury by enhancing the expression of SOCS1 and inactivating JAK/STAT signaling.
authors.affiliation: Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
authors.forename: Yucai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, P.R. China.
authors.forename: Qunfang
authors.initials: Q
authors.lastname: Rong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000473:pathology*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D050794:STAT1 Transcription Factor; C491590:Socs1 protein, mouse; C494080:Stat1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D053612:Janus Kinases