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

Jen-Kuan Chang1, William D Cornwell1, Thomas J Rogers1

  • 1Center for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.

Journal of Neuroimmunology
|May 3, 2021
PubMed

Insights

MicroRNA-21 (miR-21) expression in monocytes is induced by the μ-opioid receptor (MOR). This process involves the Ras-Raf-MEK-ERK pathway and PKCμ (PKD1), impacting pain sensitivity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Neuroscience

Background:

  • MicroRNA-21 (miR-21) is implicated in the innate immune response, particularly in the transition from inflammation to resolution.
  • The precise molecular mechanisms driving miR-21 induction are not fully understood.
  • Activation of the μ-opioid receptor (MOR) has been linked to increased miR-21 expression.

Purpose of the Study:

  • To investigate the biochemical basis for μ-opioid receptor (MOR)-mediated induction of microRNA-21 (miR-21) expression in human monocytes.
  • To identify the specific signaling pathways involved in MOR-induced miR-21 expression.

Main Methods:

  • Human monocytes were treated with μ-opioid agonists.
  • miR-21 expression levels were measured.
  • The involvement of the Ras-Raf-MEK-ERK signaling cascade and PKCμ (PKD1) was assessed.

Main Results:

  • Treatment of human monocytes with μ-opioid agonists led to a significant increase in miR-21 expression.
  • MOR-induced miR-21 expression was dependent on the activation of the Ras-Raf-MEK-ERK signaling pathway.
  • Activation of PKCμ (PKD1) was also found to be essential for MOR-mediated miR-21 induction.

Conclusions:

  • The μ-opioid receptor (MOR) pathway, involving Ras-Raf-MEK-ERK and PKCμ (PKD1), is a key regulator of miR-21 expression in monocytes.
  • These findings provide novel insights into the molecular mechanisms underlying miR-21 regulation.
  • Understanding this pathway is significant for exploring the role of miR-21 in pain sensitivity and immune responses.
Keywords:
MiR-21MonocytePKCμPKDmicroRNA

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