Abstract
Abstract Airway mucus hypersecretion and goblet cell hyperplasia plays an important role in the pathogenesis of several major airway inflammatory diseases. MUC5AC is a major component of the mucus produced by airway epithelial cells and considered to be a marker of mucus cell hyperplasia. In the study we investigate the involvement of Notch signaling in EGF-mediated expression of MUC5AC in human epithelial NCI-H292 cells. EGF stimulated the generation of Notch intracellular domain (NICD) in a RBP-Jκ-dependent manner. Treatment with γ-secretase inhibitor (GSI) or introduction of small interfering RNA directed against Notch1 reduced EGF-induced expression of MUC5AC mRNA and protein. The inhibitory effect of both GSI and Notch1 silencing on MUC5AC expression was accompanied by reduced generation of NICD and reduced expression of a Notch downstream target, Hes-1. Blockage of the Notch signaling with the two agents resulted in a decrease in ERK phosphorylation induced by EGF stimulation. ERK inhibitor inhibited MUC5AC production. These results indicate that ERK activation is necessary for Notch signaling to regulate the EGFR-mediated MUC5AC expression. Collectively, these results suggest that Notch signaling regulates the EGF-induced expression of MUC5AC through modulation of ERK activity.
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