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AMPK induces MUC5B expression via p38 MAPK in NCI-H292 airway epithelial cells

Chang Hoon Bae1, Jun Woo Kim, Sang Baik Ye

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.

Biochemical and Biophysical Research Communications
|May 31, 2011
PubMed

Insights

Adenosine monophosphate-activated protein kinase (AMPK) activates MUC5B expression in airway cells. This occurs via the p38 mitogen-activated protein kinase (MAPK) pathway, highlighting a new mechanism for mucin regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Respiratory Medicine

Background:

  • Adenosine monophosphate-activated protein kinase (AMPK) regulates cellular metabolism.
  • Emerging evidence suggests AMPK's role in modulating mucin secretion.
  • MUC5B is a key mucin involved in airway physiology.

Purpose of the Study:

  • To investigate the role and signaling pathways of AMPK in regulating MUC5B expression.
  • To determine if AMPK activation influences MUC5B expression in human airway epithelial cells.
  • To elucidate the specific MAPK pathway involved in AMPK-mediated MUC5B induction.

Main Methods:

  • Utilized NCI-H292 human airway epithelial cells.
  • Administered metformin (AMPK activator) and Compound C (AMPK inhibitor).
  • Employed adenovirus-mediated gene transfer (Ad-dnAMPK) and siRNA for pathway analysis.
  • Assessed MUC5B mRNA expression and protein phosphorylation (AMPK, p38 MAPK, ERK1/2).

Main Results:

  • Metformin dose-dependently increased MUC5B expression and AMPK phosphorylation.
  • AMPK inhibition blocked metformin-induced MUC5B expression.
  • Metformin activated p38 MAPK phosphorylation, which was crucial for MUC5B induction.
  • p38 MAPK inhibition or knockdown significantly reduced metformin-induced MUC5B expression, while ERK1/2 inhibition had no effect.

Conclusions:

  • AMPK activation induces MUC5B expression in airway epithelial cells.
  • The p38 MAPK signaling pathway mediates AMPK's effect on MUC5B.
  • This study identifies a novel AMPK-p38 MAPK signaling axis regulating MUC5B production.

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