title: House dust mite extract induces growth factor expression in nasal mucosa by activating the PI3K/Akt/HIF-1α pathway.
abstract: Growing evidence suggests that hypoxia-inducible factor-α (HIF-1α) plays an important role in the progression of allergic airway inflammation and remodeling. However, the biochemical mechanisms leading to the activation of HIF-1α and the effects of HIF-1α on the expression of growth factors, including vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and fibroblast growth factor-2 (FGF-2), in allergic nasal inflammation are not clear. We examined the relationship between HIF-1α activation and production of VEGF, TGF-β1, and FGF-2 in primary cultured nasal epithelial cells (NECs) after stimulation with house dust mite (HDM) extract. Moreover, we evaluated the importance of phosphoinositide3-kinase(PI3K)/Akt signaling in HDM-induced production of these growth factors in vitro and in the nasal mucosa of a murine model of allergic rhinitis (AR). Our results indicate HDM extract induced the expression of VEGF, TGF-β1, and FGF-2 by activating the PI3K/Akt/HIF-1α pathway in human primary cultured NECs and in the nasal mucosa of a murine model. HIF-1α regulated the expression of VEGF, TGF-β1, and FGF-2 in the nasal mucosa through direct and indirect pathways, which suggested that targeting the HIF-1α pathway could be a novel therapeutic approach for reducing nasal airway inflammation and remodeling in AR.
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China. Electronic address: zhouhan1979@sina.com.
authors.forename: Han
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology*; D065631:Rhinitis, Allergic / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Allergic rhinitis; Growth factor; Hypoxia-inducible factor 1; Nasal mucosa; PI3K; Signaling pathway