Ogremorphin inhibits GPR68 mediated MUC5AC expression

Leif R Neitzel1,2, Hussain F Basrai1,2, Charles C Hong1,2

  • 1Medicine, Michigan State University, East Lansing, Michigan, United States.

Micropublication Biology
|October 6, 2025
PubMed

Insights

Targeting the GPR68 receptor with Ogremorphin (OGM) can reduce MUC5AC mucus production. This finding offers a potential therapy for lung diseases by improving airway clearance and inhibiting tumor progression.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pulmonary Medicine

Background:

  • Mucus hypersecretion, particularly MUC5AC, worsens airway obstruction in lung diseases like asthma and aids tumor growth.
  • The pH-sensing receptor GPR68 is a key regulator of MUC5AC expression.

Purpose of the Study:

  • To investigate the role of GPR68 in mediating MUC5AC expression under acidic conditions.
  • To evaluate the efficacy of the GPR68 inhibitor Ogremorphin (OGM) in reducing MUC5AC production.

Main Methods:

  • Utilized A549 lung cancer cells to study MUC5AC mRNA and protein expression.
  • Applied acidic conditions (pH 6.4) and treated cells with OGM.
  • Confirmed GPR68's role using shRNA-mediated knockdown.

Main Results:

  • Acidification (pH 6.4) significantly increased MUC5AC mRNA and protein levels in a GPR68-dependent manner.
  • OGM treatment effectively reduced MUC5AC expression, independent of pH.
  • GPR68 knockdown corroborated the inhibitory effect of OGM on MUC5AC production.

Conclusions:

  • GPR68 signaling is crucial for MUC5AC hypersecretion.
  • GPR68 inhibition via OGM presents a promising therapeutic strategy for managing mucus hypersecretion in lung diseases.
  • This approach may improve airway clearance and limit tumor progression in pulmonary conditions.

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