Ogremorphin inhibits GPR68 mediated MUC5AC expression.

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.