miR-145 eliminates lipopolysaccharides-induced inflammatory injury in human fibroblast-like synoviocyte MH7A cells

J Cell Biochem. 2018 Dec;119(12):10059-10066. doi: 10.1002/jcb.27341. Epub 2018 Sep 7.

Abstract

Recently, it has been accepted that miR-based therapy may be beneficial for rheumatoid arthritis (RA). This study aimed to evaluate the potential involvement of miR-145 in RA in vitro. The expression of miR-145 in the human fibroblast-like synoviocyte line MH7A was overexpressed by miR-mimic transfection, after which cells were subjected to lipopolysaccharides (LPS). Cell viability, apoptosis, and the release of pro-inflammatory cytokines were measured. The result showed that the apoptosis and the release of IL-1β, IL-6, IL-8, and TNF-α were significantly induced by LPS. Meanwhile, LPS treatment led to downregulation of miR-145. miR-145 overexpression in LPS-untreated MH7A cells had no impacts on cell apoptosis and inflammation. But, restoring miR-145 expression in LPS-stimulated cells by supplementation of a miR-145 mimic protected MH7A cells against LPS-induced apoptosis and inflammation. Furthermore, miR-145 overexpression in LPS-untreated MH7A cells slightly blocked the PI3K/ATK and mTOR pathways, whereas miR-145 overexpression in LPS-stimulated cells notably repressed the LPS-induced activation of PI3K/ATK and MAPK/mTOR pathways. Our study suggested that miR-145 protected MH7A cells against LPS-induced apoptosis and inflammation by inhibiting the PI3K/AKT and MAPK/mTOR pathways.

Keywords: MH7A cell; inflammation; lipopolysaccharides (LPS); miR-145; rheumatoid arthritis (RA).

Publication types

  • Retracted Publication

MeSH terms

  • Apoptosis / genetics
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / pathology
  • Cell Line
  • Cell Survival / genetics
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Gene Expression Regulation / genetics
  • Humans
  • Inflammation / chemically induced
  • Inflammation / genetics*
  • Inflammation / pathology
  • Lipopolysaccharides / toxicity
  • MAP Kinase Kinase 1 / genetics
  • MicroRNAs / genetics*
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Signal Transduction / genetics
  • Synovial Fluid / metabolism
  • Synoviocytes / metabolism*
  • Synoviocytes / pathology
  • TOR Serine-Threonine Kinases / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Lipopolysaccharides
  • MIRN145 microRNA, human
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • MAP Kinase Kinase 1