CTGF upregulation correlates with MMP-9 level in airway remodeling in a murine model of asthma.

INTRODUCTION

Connective tissue growth factor (CTGF) mediates hypertrophy, proliferation, and extracellular matrix synthesis. Matrix metalloproteinase (MMP) plays a role in airway extracellular matrix remodeling. The correlation between CTGF and MMP in airway remodeling of asthma was unknown. This study investigated lung CTGF expression and its correlation with MMP and airway structural changes in a murine model of asthma.

MATERIAL AND METHODS

Female BALB/c mice were sensitized and challenged by intraperitoneal injections and intranasal phosphate-buffered saline (PBS) or ovalbumin (OVA). Airway responsiveness and serum OVA-specific IgE were measured. Airway structural changes were quantified by morphometric analysis. Differential cell counts and MMP-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 were evaluated in bronchoalveolar lavage fluid (BALF). Lung CTGF was determined by Western blot.

RESULTS

Serum OVA-specific IgE level and airway responsiveness in enhanced pause (Penh) is significantly higher in sensitized mice challenged with OVA compared to PBS-challenged mice. MMP-2, MMP-9, and TIMP-1 in BALF were significantly higher in OVA mice. Airway structural changes of animals' lungs with OVA challenge showed increased thickness of the smooth muscle layer and numbers of Goblet cells and inflammatory cells and eosinophils near airways and perivascular areas. Lung CTGF expression significantly increased in OVA-challenged mice. CTGF expressions positively correlated with MMP-9 ( = 0.677, < 0.05), TIMP-1 ( = 0.574, < 0.05) and thickness of the smooth muscle layer ( = 0.499, < 0.05).

CONCLUSIONS

This study indicates that CTGF upregulation correlates with MMP-9, probably involved in the pathogenesis of airway remodeling of asthma.