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 journalArticle

3 Citations (Scopus)

Abstract

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
Volume57
Issue number5
DOIs
Publication statusPublished - 2017 Nov

Fingerprint

Vascular Endothelial Growth Factor A
Permeability
Epithelium
Sinusitis
Small Interfering RNA
Epithelial Cells
Pulmonary diseases
Acoustic impedance
Respiratory Tract Diseases
Transcription
Assays
Electric Impedance
Nose
Proteins
Transcription Factors
Genes
Transfection
Monoclonal Antibodies
Hypoxia
Western Blotting

All Science Journal Classification (ASJC) codes

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

Cite this

Song, Hyun Ah ; Kim, Yoo Suk ; Cho, Hyung Ju ; Kim, Soo In ; Kang, Min Jung ; Kim, Ji Hyun ; Min, Hyun Jin ; Kang, Ju Wan ; Yoon, Joo Heon ; Kim, Chang Hoon. / Hypoxia modulates epithelial permeability via regulation of vascular endothelial growth factor in airway epithelia. In: American Journal of Respiratory Cell and Molecular Biology. 2017 ; Vol. 57, No. 5. pp. 527-535.
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Hypoxia modulates epithelial permeability via regulation of vascular endothelial growth factor in airway epithelia. / Song, Hyun Ah; Kim, Yoo Suk; Cho, Hyung Ju; Kim, Soo In; Kang, Min Jung; Kim, Ji Hyun; Min, Hyun Jin; Kang, Ju Wan; Yoon, Joo Heon; Kim, Chang Hoon.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 57, No. 5, 11.2017, p. 527-535.

Research output: Contribution to journalArticle

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AU - Song, Hyun Ah

AU - Kim, Yoo Suk

AU - Cho, Hyung Ju

AU - Kim, Soo In

AU - Kang, Min Jung

AU - Kim, Ji Hyun

AU - Min, Hyun Jin

AU - Kang, Ju Wan

AU - Yoon, Joo Heon

AU - Kim, Chang Hoon

PY - 2017/11

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N2 - 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.

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