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Abstract
BackgroundAirway mucus hypersecretion is an important pathophysiological feature in asthma. Mucins are glycoproteins that are mainly responsible for the viscoelastic property of mucus, and MUC5AC is a major mucin glycoprotein that is overproduced in asthma. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Therefore, we sought to investigate the effect of VEGF on MUC5AC expression and study the underlying mechanisms.MethodsIn order to elucidate the precise mechanism underlying the effect of VEGF on MUC5AC expression, we tested the effects of VEGF on RhoA activation and the association of caveolin-1 and VEGFR2 in Primary Bronchial Epithelial Cells.ResultsVEGF up-regulated MUC5AC mRNA and protein levels in a dose- and time-dependent manner, and activated RhoA. Additionally, VEGF-induced MUC5AC expression and RhoA activation were enhanced by disrupting caveolae with cholesterol depletion and reversed by cholesterol repletion, and inhibited by a selective VEGF receptor 2 (VEGFR2) inhibitor SU1498. Furthermore, phospho-VEGFR2 expression was decreased via overexpression of caveolin-1. VEGF treatment reduced the association of caveolin-1 and VEGFR2.ConclusionCollectively, our findings suggest that VEGF up-regulates MUC5AC expression and RhoA activation by interaction with VEGFR2, and this phenomenon was related with the association of caveolin-1 and VEGFR2. Further studies on these mechanisms are needed to facilitate the development of treatments for asthma.
Highlights
Airway mucus hypersecretion is an important pathophysiological feature in asthma
Vascular endothelial growth factor (VEGF) up-regulates MUC5AC expression in primary bronchial epithelial cells (PBECs) To evaluate the effect of VEGF on MUC5AC expression, we performed real-time PCR in PBECs
When PBECs were treated with various doses of VEGF for different times, MUC5AC mRNA expression was up-regulated in a dose- and time-dependent manner (Fig. 1a,b), suggesting that VEGF up-regulates MUC5AC mRNA expression in PBECs
Summary
Airway mucus hypersecretion is an important pathophysiological feature in asthma. Mucins are glycoproteins that are mainly responsible for the viscoelastic property of mucus, and MUC5AC is a major mucin glycoprotein that is overproduced in asthma. Airway mucus hypersecretion is recognized as an important pathophysiological feature in asthma [1]. Mucins are glycoproteins that are mainly responsible for the viscoelasticity of the mucus. MUC5AC is a major mucin glycoprotein and is overproduced in asthma [2, 3]. Recent data indicated that cultured primary bronchial epithelial cells (PBECs) of asthmatics had lower caveolin-1 expression compared to that in the control cells [5]. In vitro studies revealed that IL-4 causes aggregation of caveolin-1-containing lipid rafts, resulting in increased MUC5AC synthesis in bronchial epithelial cells
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