AP2α is essential for MUC8 gene expression in human airway epithelial cells

Uk Yeol Moon, Chang Hoon Kim, Jae Young Choi, Yoon Ju Kim, Yeon Ho Choi, Ho Geun Yoon, Hyeyoung Kim, Joo Heon Yoon

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Abstract

Mucins are high molecular weight proteins that make up the major components of mucus. Hypersecretion of mucus is a feature of several chronic inflammatory airway diseases. MUC8 is an important component of airway mucus, and its gene expression is upregulated in nasal polyp epithelium. Little is known about the molecular mechanisms of MUC8 gene expression. We first observed overexpression of activator protein-2alpha (AP2a) in human nasal polyp epithelium. We hypothesized that AP2a overexpression in nasal polyp epithelium correlates closely with MUC8 gene expression. We demonstrated that phorbol 12-myristate 13-acetate (PMA) treatment of the airway epithelial cell line NCI-H292 increases MUC8 gene and AP2a expression. In this study, we sought to determine which signal pathway is involved in PMAinduced MUC8 gene expression. The results show that the protein kinase C and mitogen-activating protein/ERK kinase (MAPK) pathways modulate MUC8 gene expression. PD98059 or ERK1/2 siRNA and RO-31-8220 or PKC siRNA significantly suppress AP2a as well as MUC8 gene expression in PMA-treated cells. To verify the role of AP2a, we specifically knocked down AP2a expression with siRNA. A significant AP2a knock-down inhibited PMA-induced MUC8 gene expression. While dominant negative AP2a decreased PMA-induced MUC8 gene expression, overexpressing wildtype AP2a increased MUC8 gene expression. Furthermore, using lentiviral vectors for RNA interference in human nasal polyp epithelial cells, we confirmed an essential role for AP2a in MUC8 gene expression. From these results, we concluded that PMA induces MUC8 gene expression through a mechanism involving PKC, ERK1/2, and AP2a activation in human airway epithelial cells.

Original languageEnglish
Pages (from-to)1386-1398
Number of pages13
JournalJournal of Cellular Biochemistry
Volume110
Issue number6
DOIs
Publication statusPublished - 2010 Aug 15

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Moon, U. Y., Kim, C. H., Choi, J. Y., Kim, Y. J., Choi, Y. H., Yoon, H. G., Kim, H., & Yoon, J. H. (2010). AP2α is essential for MUC8 gene expression in human airway epithelial cells. Journal of Cellular Biochemistry, 110(6), 1386-1398. https://doi.org/10.1002/jcb.22655