MiR-183 delivery attenuates murine lupus nephritis-related injuries via targeting mTOR

Scand J Immunol. 2019 Nov;90(5):e12810. doi: 10.1111/sji.12810. Epub 2019 Sep 5.

Abstract

MicroRNAs (miRNAs) play a vital role in the occurrence and development of many human diseases, including systemic lupus erythematosus (SLE). SLE is an autoimmune disease characterized by the production of autoantibodies against nuclear antigens and multiorgan involvement. Study of miRNAs involved in SLE provides new insights into the pathogenesis of SLE and might lead to the identification of new therapeutic interventions. The aim of this study was to investigate the effect of miR-183 injection on the progression of SLE by using MRL/lpr mouse model. The expression levels of miR-183 and mTOR mRNA were detected by quantitative real-time PCR assay. The effect of miR-183 on the course of spontaneous disease progression in the MRL/lpr mice was examined by intraperitoneal injection of miR-183 into mice and followed by monitoring lifespan, anti-dsDNA antibody levels, urinary albumin levels, blood urea nitrogen (BUN) levels, and Tregs and Th17 cell population. We found that miR-183 injection resulted in reduction of anti-DNA antibody and immune complex component levels, restoration of Tregs and Th17 cell population and prolongation of survival. Our findings suggest that miR-183 injection may serve as an effective therapeutic treatment for delaying or easing pathologic features of SLE.

Keywords: lupus nephritis; mTOR; miR-183; miRNAs-based therapy; systemic lupus erythematosus.

MeSH terms

  • Adult
  • Albuminuria / urine
  • Animals
  • Antibodies, Antinuclear / blood
  • Blood Urea Nitrogen
  • Disease Models, Animal
  • Female
  • Humans
  • Lupus Nephritis / genetics
  • Lupus Nephritis / therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • MicroRNAs / therapeutic use*
  • RNA, Messenger / genetics
  • T-Lymphocytes, Regulatory / immunology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism
  • Th17 Cells / immunology

Substances

  • Antibodies, Antinuclear
  • MIRN183 microRNA, human
  • MicroRNAs
  • Mirn183 microRNA, mouse
  • RNA, Messenger
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse