Insulin-like growth factor-1 induces MUC8 and MUC5B expression via ERK1 and p38 MAPK in human airway epithelial cells

Abstract

The biologic actions of insulin-like growth factor-1(IGF-1) are associated with cell growth, differentiation, migration, and survival. IGF-1 constitutes the pathogenic factor in formation of nasal polyps and the regulatory factor in expression of mucins. However, the effect of IGF-1 on MUC8 and MUC5B expression has not been reported. Therefore, in this study, the effect and brief signaling pathway of IGF-1 on MUC8 and MUC5B expression were investigated in human airway epithelial cells. In mucin-producing human NCI-H292 airway epithelial cells and the primary cultures of normal human nasal epithelial cells, the effect and signaling pathway of IGF-1 on MUC8 and MUC5B expression were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA (siRNA) for mitogen-activated protein kinase (MAPK). IGF-1 induced MUC8 and MUC5B expression, and activated phosphorylation of ERK1/2 and p38 MAPK. U0126 (ERK1/2 inhibitor) and SB203580 (p38 MAPK inhibitor) inhibited IGF-1 induced MUC8 and MUC5B mRNA expression. In addition, the knockdown of ERK1 and p38 MAPK by siRNA significantly blocked IGF-1 induced MUC8 and MUC5B mRNA expression; the knockdown of ERK2 MAPK by siRNA did not. These results demonstrate for the first time that IGF-1 induced MUC8 and MUC5B expression is regulated by activation of the ERK1 and p38 MAPK signaling pathway in human airway epithelial cells.