MicroRNA-467b targets LPL gene in RAW 264.7 macrophages and attenuates lipid accumulation and proinflammatory cytokine secretion

Biochimie. 2012 Dec;94(12):2749-55. doi: 10.1016/j.biochi.2012.08.018. Epub 2012 Aug 31.

Abstract

LPL (lipoprotein lipase) is a rate-limiting enzyme involved in the hydrolysis of triglycerides. Previous studies have shown that microRNA (miR)-467b regulates hepatic LPL expression and plays a role in the progression of steatosis or abnormal lipid retention in obese mice. Macrophage-derived LPL has been shown to promote atherosclerosis. However, if miR-476b influences macrophage LPL expression and the subsequent effects are unknown. Here, we utilized oxLDL-treatment RAW 264.7 macrophages that were transfected with miR-467b mimics or inhibitors to investigate the potential roles of macrophage miR-476b. We found that miR-467b significantly decreased lipid accumulation and IL-6, IL-1β, TNF-α and MCP-1 secretions. Furthermore, our studies suggested an additional explanation for the regulatory mechanism of miR-467b on its functional target, LPL in RAW 264.7 macrophages. Thus, our findings indicate that miR-467b may regulate lipid accumulation and proinflammatory cytokine secretion in oxLDL-stimulated RAW 264.7 macrophages by targeting the LPL gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Line
  • Chemokine CCL2 / metabolism
  • Chromatography, High Pressure Liquid
  • Cytokines / metabolism*
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lipid Metabolism / drug effects
  • Lipids / analysis*
  • Lipoprotein Lipase / genetics*
  • Lipoprotein Lipase / metabolism
  • Lipoproteins, LDL / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 3' Untranslated Regions
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Cytokines
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Lipids
  • Lipoproteins, LDL
  • MIRN467 microRNA, mouse
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • oxidized low density lipoprotein
  • Lipoprotein Lipase