Vascular endothelial growth factor modulates matrix metalloproteinase-9 expression in asthma.
BACKGROUND
Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are mediators of airway inflammation and remodeling in asthma.


OBJECTIVE
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.


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.
Lee
Kyung Sun
KS
Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Geumam-dong, Deokjin-gu, Jeonju, Jeonbuk 561-180, Republic of Korea.
Min
Kyung Hoon
KH
Kim
So Ri
SR
Park
Seoung Ju
SJ
Park
Hee Sun
HS
Jin
Gong Yong
GY
Lee
Yong Chul
YC
D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002934:Cinnamates / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000097:blood; D010047:Ovalbumin / Q000276:immunology; D013183:Sputum / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
D002934:Cinnamates; D007211:Indoles; D018793:Interleukin-13; D015848:Interleukin-5; C483044:SU 1498; C416849:SU 5614; D042461:Vascular Endothelial Growth Factor A; D015847:Interleukin-4; D010047:Ovalbumin; D040301:Vascular Endothelial Growth Factor Receptor-2; D020780:Matrix Metalloproteinase 9