title: 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.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Bae
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Si-Youn
authors.initials: SY
authors.lastname: Song
authors.forename: Yong-Woon
authors.initials: YW
authors.lastname: Kim
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
mesh_terms: D002460:Cell Line; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055257:Mucin-5B / Q000096:biosynthesis*; D009077:Mucins / Q000096:biosynthesis*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; C524578:MUC5B protein, human; C105059:MUC8 protein, human; D055257:Mucin-5B; D009077:Mucins; D011725:Pyridines; D007334:Insulin-Like Growth Factor I; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580