Published ahead of print on April 27, 2006, doi:10.1164/rccm.200510-1558OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200510-1558OC
Vascular Endothelial Growth Factor Modulates Matrix Metalloproteinase-9 Expression in AsthmaDepartment of Internal Medicine, Department of Radiology, Airway Remodeling Laboratory, and Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, Jeonju, Republic of Korea Correspondence and requests for reprints should be addressed to Yong Chul Lee, M.D., Ph.D., Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk 561-180, Republic of Korea. E-mail: leeyc{at}chonbuk.ac.kr 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.
Key Words: airway inflammation • extracellular matrix • permeability • remodeling This article has been cited by other articles:
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