Ogremorphin inhibits GPR68 mediated MUC5AC expression.

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.