Hypoxia modulates epithelial permeability via regulation of vascular endothelial growth factor in airway epithelia

Hyun Ah Song, Yoo Suk Kim, Hyung Ju Cho, Soo In Kim, Min Jung Kang, Ji Hyun Kim, Hyun Jin Min, Ju Wan Kang, Joo Heon Yoon, Chang Hoon Kim

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Hypoxia resulting from occlusion of the sinus ostium is known to be one of the major pathogenic mechanisms of sinusitis. Hypoxiainducible factor (HIF)-1 is a widely known transcription factor that induces the cellular response to hypoxic conditions and activates the transcription of several genes, including vascular endothelial growth factor (VEGF).We hypothesized that induced permeability caused by hypoxia is a major pathophysiologic mechanism of upper airway diseases, such as sinusitis. The aim of this study was to investigate the mechanism of hypoxia-induced hyperpermeability, which mediates increased paracellular permeability and enhanced microbial invasiveness in the airway epithelium.We show that expression ofVEGFmRNAand protein andHIF-1a protein increased as a function of time under hypoxia in normal human nasal epithelial cells. Our results also indicate that VEGF expression was induced by transfectionwith amammalian expressionvector encoding HIF-1 but down-regulated by transfection with small interfering RNA specific for HIF-1a under hypoxic conditions. Results of a transepithelial permeability assay measuring transepithelial electrical resistance indicated that permeability was increased as a function of time under hypoxia and was rescued by anti-VEGF monoclonal antibody (bevacizumab) and small interfering RNA specific for HIF-1a.We detected up-regulated HIF-1a and VEGF expression in mucosal epithelium samples from patients with sinusitis compared with normal mucosal epithelium using Western blotting and immunohistochemical staining. In conclusion, we suggest that the hypoxia-HIF-1a-VEGF axis plays an important role in hyperpermeability of airway epithelial cells, implying a role in the pathophysiology of upper respiratory tract diseases, such as sinusitis.

Original languageEnglish
Pages (from-to)527-535
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number5
Publication statusPublished - 2017 Nov

Bibliographical note

Publisher Copyright:
Copyright © 2017 by the American Thoracic Society.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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