Defective expression of the regulator of G-protein signaling (RGS) 4 increases MUC5AC overproduction in the epithelia of nasal polyps

Abstract

Nasal polyps are believed that they may be caused by allergy and cystic fibrosis. Despite elimination by surgery, nasal polyps are observed to recur about 70%. Most importantly, the pathogenesis of nasal polyps has been unknown. Therefore, the molecular mechanisms that increase mucous hypersecretion in nasal polyps should be identified. The understanding of these mechanisms is important for developing new therapeutic strategies. The aim of this study was to identify the effect of the regulator of G protein signaling 4 protein (RGS4) on nasal polyps and to investigate the role of the ATP-sensitive potassium (K-ATP) channel on lipopolysaccharide (LPS)-induced mucin-5AC protein (MUC5AC) expression in vivo. MUC5AC and RGS4 expressions were studied by immunoblotting in human nasal polyp and in lungs from Rgs4 knock-out mice. Glybenclamide and apyrase were challenged i.p. injection for 2 hr in prior to LPS instillation using tracheostomy. We found that the expression of RGS4 was dramatically suppressed to about 70% in the polyp specimens compared to that in the normal nasal mucosa. This finding suggests that defective RGS4 expression may have a role in the increased MUC5AC expression in the epithelia of human nasal polyps. Inhibition of the K-ATP channel leads to diminished MUC5AC overexpression in vivo. Since the K-ATP channel can be mediated in LPS-induced MUC5AC expression in vivo, the K-ATP channel may be a good target for regulating mucous hypersecretion in respiratory diseases.