title: MiR-212-3p inhibits LPS-induced inflammatory response through targeting HMGB1 in murine macrophages.
abstract: Sepsis is a major cause of mortality in seriously ill patients characterized by a series of severe systemic inflammatory responses due to an infection. Thus, there is a critically need to search more accurate biomarkers and targets for diagnosis and treatment of sepsis. Our study showed that miR-212-3p was up-regulated in LPS-treated macrophage RAW264.7 cells. Overexpression of miR-212-3p in RAW264.7 cells led to suppression of pro-inflammatory cytokines (TNF-α and IL-6) induced by LPS. Bioinformatic predictions and experimental researches both revealed that HMGB1 was a direct target of miR-212-3p. Meanwhile, the results showed that overexpression of miR-212-3p inhibited the cytoplasmic translocation of HMGB1 in LPS-induced RAW264.7 cells. Subsequently, transfection of the pcDNA3.1/HMGB1 plasmid, which produced HMGB1 overexpression, exhibited similar effects as the LPS-induced macrophage inflammatory response and markedly activated the MAPKs including p38, ERK and JNK phosphorylation. Furthermore, we also found that the phosphorylation of p38 MAPK and ERK was downregulated by miR-212-3p mimics upon LPS injection. In conclusion, these results reveal that miR-212-3p directly targets HMGB1 to suppress inflammatory response in LPS-induced RAW264.7 cells. All our findings indicate that miR-212-3p may act as a potential pharmacological target for promising and effective therapeutic intervention in microbial infection in the future.
authors.affiliation: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of pharmacy, East China University of Science and Technology, Shanghai, PR China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of pharmacy, East China University of Science and Technology, Shanghai, PR China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of pharmacy, East China University of Science and Technology, Shanghai, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, PR China. Electronic address: lqf989@163.com.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of pharmacy, East China University of Science and Technology, Shanghai, PR China. Electronic address: xin.liang@ecust.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of pharmacy, East China University of Science and Technology, Shanghai, PR China. Electronic address: liujian@ecust.edu.cn.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; C554518:MIRN212 microRNA, mouse; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha
keywords: HMGB1; Inflammatory response; MAPKs; MiR-212-3p