Growing evidence suggests that hypoxia-inducible factor -alpha (HIF-1 alpha) plays an important role in the progression of allergic airway inflammation and remodeling. However, the biochemical mechanisms leading to the activation of HIF-1 alpha and the effects of HIF-1 alpha on the expression of growth factors, including vascular endothelial growth factor (VEGF), transforming growth factor-beta 1 (TGF-(beta 1), and fibroblast growth factor-2 (FGF-2), in allergic nasal inflammation are not clear. We examined the relationship between HIF-1 alpha activation and production of VEGF, TGF-beta 1, 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-beta 1, and FGF-2 by activating the PI3K/Akt/HIF-1 alpha pathway in human primary cultured NECs and in the nasal mucosa of a murine model. HIF-1 alpha regulated the expression of VEGF, TGF-beta 1, and FGF-2 in the nasal mucosa through direct and indirect pathways, which suggested that targeting the HIF-1 alpha pathway could be a novel therapeutic approach for reducing nasal airway inflammation and remodeling in AR. (C) 2015 Elsevier Inc. All rights reserved.