Vascular endothelial growth factor modulates matrix metalloproteinase-9 expression in asthma

Sun Lee Kyung, Kyung-Hoon Min, Ri Kim So, Ju Park Seoung, Sun Park Hee, Yong Jin Gong, Chul Lee Yong

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Rationale: Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are mediators of airway inflammation and remodeling in asthma. Objectives: This study investigates a potential relationship between VEGF and MMP-9, and the mechanisms by which VEGF signaling regulates MMP-9 expression in asthma. Methods: We evaluated whether levels of VEGF correlated with levels of MMP-9 in the sputum of asthma patients, and the effect of VEGF receptor inhibitors on MMP-9 expression in murine model of asthma. Measurements and Main Results: We have found that levels of VEGF and MMP-9 are significantly higher in the sputum of patients with asthma than in healthy control subjects, and a significant correlation is found between the levels of VEGF and MMP-9. This study with the ovalbumin-induced model of asthma revealed the following typical pathophysiologic features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of MMP-9 and VEGF. Administration of VEGF receptor inhibitors reduced the pathophysiologic signs of asthma and decreased the increased expression of MMP-9 after ovalbumin inhalation. Conclusions: These results indicate that there is a close relationship between VEGF and MMP-9 expression and that inhibition of VEGF receptor down-regulates the expression of MMP-9. These findings suggest that VEGF signaling regulates MMP-9 expression and plays a critical role in initiation and maintenance of asthma.

Original languageEnglish
Pages (from-to)161-170
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume174
Issue number2
DOIs
Publication statusPublished - 2006 Jul 13
Externally publishedYes

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Keywords

  • Airway inflammation
  • Extracellular matrix
  • Permeability
  • Remodeling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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