title: NDRG1 is important to maintain the integrity of airway epithelial barrier through claudin-9 expression.
abstract: Impairment of epithelial barrier integrity caused by environmental triggers is associated with the pathogenesis of airway inflammation. Using human airway epithelial cells, we attempted to identify molecule(s) that promote airway epithelial barrier integrity. Microarray analyses were conducted using the Affimetrix human whole genome gene chip, and we identified the N-myc downstream-regulated gene 1 (NDRG1) gene, which was induced during the development of the epithelial cell barrier. Immunohistochemical analysis revealed strong NDRG1 expression in ciliated epithelial cells in nasal tissues sampled from patients with chronic rhinosinusitis (CRS), and the low expression of NDRG1 was observed in goblet cells or damaged epithelial cells. NDRG1 gene knockdown with its specific siRNA decreased the transepithelial electrical resistance and increased the dextran permeability. Immunocytochemistry revealed that NDRG1 knockdown disrupted tight junctions of airway epithelial cells. Next, we analyzed the effects of NDRG1 knockdown on the expression of tight and adhesion junction molecules. NDRG1 knockdown significantly decreased only claudin-9 expression, but did not decrease other claudin family molecules, such as E-cadherin, and ZO-1, -2, or -3. Knockdown of claudin-9 markedly impaired the barrier function in airway epithelial cells. These results suggest that NDRG1 is important for the barrier integrity in airway epithelial cells.
authors.affiliation: Division of Respiratory Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.|Division of Otolaryngology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Gon
authors.affiliation: Division of Respiratory Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Maruoka
authors.affiliation: Division of Otolaryngology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishi
authors.affiliation: Division of Respiratory Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kozu
authors.affiliation: Division of Microbiology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Kuroda
authors.initials: K
authors.lastname: Kazumichi
authors.affiliation: Division of Otolaryngology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: Division of Respiratory Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Takeshita
authors.affiliation: Division of Otolaryngology, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Division of Respiratory Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo 173-8610, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D015703:Antigens, CD; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D001991:Bronchitis / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D057167:Claudins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D018797:Cell Cycle Proteins; D057167:Claudins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C513384:CDH1 protein, human; C524757:CLDN9 protein, human
keywords: NDRG1; barrier function; chronic rhinosinusitis; claudin-9; tight junction