The μ-opioid receptor induces miR-21 expression and is ERK/PKCμ-dependent

J Neuroimmunol. 2021 Jul 15:356:577585. doi: 10.1016/j.jneuroim.2021.577585. Epub 2021 Apr 24.

Abstract

Micro RNA-21 (miR-21) is believed to perform an important role in the transition from inflammation to resolution in the innate immune response. The biochemical basis for the induction of miR-21 remains uncertain. However, the activation of the μ-opioid receptor (MOR) induces the expression of miR-21. Our results show that human monocytes treated with μ-opioid agonists exhibit a significant increase in miR-21 expression. We found that MOR-induction of miR-21 requires the activation of the Ras-Raf-MEK-ERK signaling cascade, and to our surprise, the activation of PKCμ (PKD1). These results are significant given the role of miR-21 in the sensitivity to pain.

Keywords: MiR-21; Monocyte; PKCμ; PKD; microRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Receptors, Opioid, mu / biosynthesis*
  • Receptors, Opioid, mu / genetics

Substances

  • Analgesics, Opioid
  • MIRN21 microRNA, human
  • MicroRNAs
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • protein kinase D
  • Protein Kinase C