Effects of Several Drugs for Metabolic Syndrome on Phorbol Ester- or Epidermal Growth Factor-induced Gene Expression and Production of Airway MUC5AC Mucin: Investigation of Potential Regulator for Hypersecretion of Airway Mucus using Drug Repositioning Strategy

Abstract

We investigated whether rosiglitazone, metformin, thioctic acid, simvastatin, or glimepiride affects airway MUC5AC mucin gene transcription or protein expression induced by phorbol 12-myristate 13-acetate (PMA) or epidermal growth factor (EGF) in NCI-H292 cells. Cells were pretreated with each agent for 30 min, then stimulated with PMA or EGF for 24 h. Of the five agents, rosiglitazone inhibited PMA-induced gene transcription and production of MUC5AC mucin in NCI-H292 cells. This result suggests that rosiglitazone, an antidiabetic peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, can inhibit PMA-induced mucin expression at mRNA and protein levels, through directly acting on airway epithelial cells.