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Published on: June 14, 2016
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.
Abstract:
MUC5AC hypersecretion exacerbates airway obstruction in lung diseases, such as asthma, and promotes tumor growth. The expression of MUC5AC is driven by the pH-sensing receptor, GPR68. Herein we demonstrate that acidification (pH 6.4) increased MUC5AC mRNA and protein expression in a GPR68-dependent manner in A549 cells. Treatment with Ogremorphin (OGM), a specific GPR68 inhibitor, reduced MUC5AC mRNA and protein expression irrespective of pH. These findings were confirmed by shRNA-mediated knockdown of GPR68. These data suggest GPR68 inhibition by OGM as a potential therapy for mucus hypersecretion to improve airway clearance and reduce tumor progression in lung diseases.
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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