Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
Biochem Biophys Res Commun. 2013 Jan 11;430(2):683-8. doi: 10.1016/j.bbrc.2012.11.091. Epub 2012 Dec 2.
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.
胰岛素样生长因子-1(IGF-1)的生物学作用与细胞生长、分化、迁移和存活有关。IGF-1 是鼻息肉形成的致病因素，也是粘蛋白表达的调节因子。然而，IGF-1 对 MUC8 和 MUC5B 表达的影响尚未报道。因此，本研究旨在探讨 IGF-1 对人呼吸道上皮细胞 MUC8 和 MUC5B 表达的作用及其简要信号通路。在粘蛋白产生的人 NCI-H292 气道上皮细胞和正常人鼻黏膜上皮细胞的原代培养物中，采用逆转录-聚合酶链反应(RT-PCR)、实时 PCR、酶免疫分析和免疫印迹分析，用丝裂原活化蛋白激酶（MAPK）的特异性抑制剂和小干扰 RNA（siRNA）研究 IGF-1 对 MUC8 和 MUC5B 表达的影响及其信号通路。IGF-1 诱导 MUC8 和 MUC5B 表达，并激活 ERK1/2 和 p38 MAPK 的磷酸化。U0126（ERK1/2 抑制剂）和 SB203580（p38 MAPK 抑制剂）抑制 IGF-1 诱导的 MUC8 和 MUC5B mRNA 表达。此外，siRNA 敲低 ERK1 和 p38 MAPK 显著阻断 IGF-1 诱导的 MUC8 和 MUC5B mRNA 表达；siRNA 敲低 ERK2 MAPK 则没有阻断。这些结果首次表明，IGF-1 诱导 MUC8 和 MUC5B 表达是通过激活人呼吸道上皮细胞中的 ERK1 和 p38 MAPK 信号通路来调节的。
