MicroRNA-221 regulates endothelial nitric oxide production and inflammatory response by targeting adiponectin receptor 1

Gene. 2015 Jul 10;565(2):246-51. doi: 10.1016/j.gene.2015.04.014. Epub 2015 Apr 9.

Abstract

Adiponectin exerts anti-atherosclerosis property through its 2 receptors (AdipoR1 and AdipoR2). The mechanism regulating the expression of adiponectin receptors is unclear. Bioinformatics analysis showed that miR-221 targeted the 3'-untranslated region (3'UTR) of the AdipoR1 mRNA. The protein level and the mRNA level of AdipoR1 were reduced when miR-221 was expressed in human umbilical vein endothelial cells (HUVECs). Meanwhile, miR-221 repressed the activity of luciferase reporter containing the 3'UTR of AdipoR1. The inhibitory effect of miR-221 was abolished when the miR-221 binding site within the AdipoR1 3'UTR was deleted. Overexpression of miR-221 inhibited adiponectin-stimulated nitric oxide (NO) production in HUVECs. Furthermore, miR-221 abolished the inhibitory effect of adiponectin on NF-kB activation and the expression of adhesion molecules. Altogether, these results indicated that miR-221 targets AdipoR1 to regulate endothelial inflammatory response.

Keywords: AdipoR1; Adiponectin; NF-kB; NO; miR-221.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adiponectin / genetics
  • Adiponectin / metabolism
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Cell Line
  • Computational Biology / methods
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • MicroRNAs / genetics*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / genetics*
  • Nitric Oxide / metabolism*
  • RNA, Messenger / genetics
  • Receptors, Adiponectin / genetics
  • Receptors, Adiponectin / metabolism

Substances

  • 3' Untranslated Regions
  • ADIPOR1 protein, human
  • ADIPOR2 protein, human
  • Adiponectin
  • MIRN221 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Adiponectin
  • Nitric Oxide