MicroRNA-124 inhibits macrophage cell apoptosis via targeting p38/MAPK signaling pathway in atherosclerosis development

Aging (Albany NY). 2020 Jun 30;12(13):13005-13022. doi: 10.18632/aging.103387. Epub 2020 Jun 30.

Abstract

The objective of this study is to characterize the function of microRNA (miR)-124 in the process of coronary artery disease (CAD). Eighty patients, including 40 CAD patients and 40 non-CAD control patients were enrolled in this study. Atherosclerosis model was established in vivo in ApoE-/- mice and in vitro in RAW264.7 cells. Expression of miR-124 and p38 in patients, animal models and cell models were measured by qRT-PCR, western blot and immunohistochemistry assay. Overexpression or suppression of miR-124 was introduced in vitro and in vivo and the expression levels of p38, miR-124, pro- and anti-inflammatory cytokines, and pro- and anti-apoptotic factors were examined. Results showed that miR-124 was decreased, while p38 was increased in CAD patients and atherosclerosis models compared with control group. MiR-124 could target p38 by binding its 3' untranslated region and negatively regulated the protein expression of p38. Overexpression of miR-124 increased the expression of anti-inflammatory cytokines, reduced the expression of pro- inflammatory cytokines, and inhibited macrophage apoptosis. MiR-124 overexpression may be a promising treatment for atherosclerosis and CAD via inhibiting p38.

Keywords: apoptosis; atherosclerosis; inflammatory response; macrophage; miR-124; p38.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / physiology*
  • Atherosclerosis / metabolism*
  • Cells, Cultured
  • Coronary Artery Disease / metabolism
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Macrophages / metabolism
  • Male
  • Mice
  • MicroRNAs / analysis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RAW 264.7 Cells
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • MIRN124 microRNA, human
  • MicroRNAs
  • Mirn124 microRNA, mouse
  • p38 Mitogen-Activated Protein Kinases