Novel involvement of miR-522-3p in high-mobility group box 1-induced prostaglandin reductase 1 expression and reduction of phagocytosis

Biochim Biophys Acta Mol Cell Res. 2017 Apr;1864(4):625-633. doi: 10.1016/j.bbamcr.2017.01.006. Epub 2017 Jan 11.

Abstract

Resolution of inflammation is important for physiological homeostasis. Chronic inflammatory diseases may be caused by abnormal resolution of inflammation. However, what causes a failure of inflammatory resolution is unclear. Here we investigated the involvement of high mobility group box 1 (HMGB1) protein in the control of inflammatory resolution as an 'anti-resolution factor'. We first confirmed the increased expression of HMGB1 and prostaglandin reductase 1 (PTGR1) in inflammatory conditions and HMGB1-mediated regulation of the expression of PTGR1. The inhibition of phagocytosis by HMGB1 was abrogated by PTGR1 silencing. PTGR1 was a direct target of miR522-3p and its expression was regulated by miRNA-522-3p inhibitor or mimic. Finally, miR-522-3p had an important role in the regulation of PTGR1 expression by HMGB1. The data indicates that HMGB1-miR-522-3p-PTGR1 axis may be involved in the abnormal resolution of inflammation and suggests that this mechanism might be a target for modulation of chronic inflammatory disorder.

Keywords: Antiresolution factor; HMGB1; Inflammation; PTGR1; Phagocytosis; miR-522-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / antagonists & inhibitors
  • Alcohol Oxidoreductases / genetics*
  • Alcohol Oxidoreductases / metabolism
  • Base Sequence
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Gene Expression Regulation
  • HMGB1 Protein / genetics*
  • HMGB1 Protein / metabolism
  • Humans
  • Inflammation
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / pathology
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Monocytes / cytology
  • Monocytes / metabolism
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Phagocytosis / drug effects
  • Phagocytosis / genetics*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • HMGB1 Protein
  • HMGB1 protein, human
  • Lipopolysaccharides
  • MIRN522 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • RNA, Small Interfering
  • Alcohol Oxidoreductases
  • leukotriene B4 12-hydroxydehydrogenase
  • Tetradecanoylphorbol Acetate