Dysregulation of microRNA-657 influences inflammatory response via targeting interleukin-37 in gestational diabetes mellitus

J Cell Physiol. 2019 May;234(5):7141-7148. doi: 10.1002/jcp.27468. Epub 2018 Oct 26.

Abstract

A number of studies have implicated that microRNAs (miRNAs) play a critical role in the development of gestational diabetes mellitus (GDM). However, the role of miR-657 in GDM remains vague up to date. We aim to investigate the modifying effect of miR-657 on GDM, which will provide new insight into the pathogenesis of GDM and may help to identify new diagnostic or therapeutic targets for GDM. Increased expression of miR-657 but decreased expression of interleukin-37 (IL-37) was observed in patients with GDM. Besides, negative association between miR-657 and IL-37 was demonstrated in this study. miR-657 could targetedly regulate IL-37 and enhance the proliferation of mononuclear macrophages. Moreover, miR-657 promoted the generation of inflammatory cytokines (IL-6 and tumor necrosis factor-α [TNF-α]) and activation of nuclear factor κB (NF-κB) in lipopolysaccharide-induced mononuclear macrophages, while its effect was significantly inhibited when exogenous recombinant IL-37 was administrated into cells. Accordingly, dysregulation of miR-657 contributes to the pathogenesis of GDM via IL-37/NF-κB signaling axis.

Keywords: IL-37; NF-κB; gestational diabetes mellitus; inflammation; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cell Proliferation
  • Diabetes, Gestational / genetics
  • Diabetes, Gestational / immunology
  • Diabetes, Gestational / metabolism*
  • Female
  • Gene Expression Regulation
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism*
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism
  • Placenta / immunology
  • Placenta / metabolism*
  • Pregnancy
  • Signal Transduction
  • THP-1 Cells

Substances

  • IL37 protein, human
  • Inflammation Mediators
  • Interleukin-1
  • MIRN657 microRNA, human
  • MicroRNAs
  • NF-kappa B