title: 1,25-Dihydroxyvitamin D3targeting VEGF pathway alleviates house dust mite (HDM)-induced airway epithelial barrier dysfunction.
abstract: In our previous studies, we have indentified that 1,25-dihydroxyvitamin D3(1,25(OH)2D3) can alleviate toluene diisocyanate-induced airway epithelial barrier disruption and we also found that vascular endothelial growth factor (VEGF) derived from airway epithelials cells could disrupt epithelial barrier.
  
  
  
  The study aimed to investigate whether 1,25(OH)2D3can inhibit house dust mite (HDM) induced airway epithelial barrier dysfunction by regulating the VEGF pathway.
  
  
  
  The 16HBE and BEAS-2B cells were cultured and treated according to the experiment requirement. Trans Epithelial Electric Resistance (TEER), permeability of epithelial layer, and distribution and expression of junction proteins were used to evaluate the cell layer barrier function, Western Blot was used to evaluate the expression of junction proteins and phosphorylated Akt in the cells, RT-PCR and ELISA were used to evaluate the VEGF gene expression and protein release in the cells. Recombinant VEGF165 was used to determine the role of the VEGF pathway in the epithelial barrier function.
  
  
  
  HDM resulted in a decline in TEER and increase of cell permeability, following abnormal distribution and expression of junction proteins (E-Cadherin and zona occludens (ZO)-1), accompanied by a significant upregulation of VEGF and phosphorylated Akt, which were all partly recovered by treatment with either 1,25(OH)2D3or PI3K inhibitor LY294002. VEGF165-induced barrier dysfunction was accompanied by disruption of the epithelial E-cadherin and β-catenin, pretreatment of 1,25(OH)2D3and LY294002 markedly attenuated VEGF-induced airway barrier disruption in 16HBE cells.
  
  
  
  1,25(OH)2D3can alleviate HDM-induced airway epithelial barrier dysfunction by inhibiting PI3K pathway-dependent VEGF release.
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ruhui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hangming
authors.initials: H
authors.lastname: Dong
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Haijin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: caishaox@fimmu.com.
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D039741:Antigens, Dermatophagoides / Q000276:immunology; D015820:Cadherins / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D017097:Electric Impedance; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D039981:Pyroglyphidae; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018926:Anti-Allergic Agents; D039741:Antigens, Dermatophagoides; D015820:Cadherins; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D002117:Calcitriol
keywords: 1,25(OH)(2)D(3); Airway epithelial barrier; Asthma; HDM; PI3K/AKT pathway phosphorylation; VEGF