Increased Levels of CTGF mRNA Expression in a Murine Model of Allergic Airway Inflammation

Abstract

Background: Connective tissue growth factor (CTGF) is known to play a direct role in fibrosis in various organs as a downstream mediator of TGF-β. Objective: To evaluate a role in subepithelial fibrosis in the asthmatic airway, we investigated CTGF mRNA expression and CTGF producing cells in the airways of a murine asthma model with allergic inflammation. Methods: After repetitive inhalation challenges with ovalbumin (OVA), cell numbers and TGF-β1 concentrations in bronchoalveolar lavage fluid from immunized mice were measured. Collagen deposition in lung tissue was estimated by measuring hydroxyproline content. CTGF mRNA and GAPDH mRNA levels were determined by quantitative RT-PCR method. Immunohistochemistry for CTGF with anti-CTGF antibody was performed. Results: Numbers of eosinophils and TGF-β1 concentration increased markedly in BALF on the 7th day and 14th day after inhalation challenge with OVA. Hydroxyproline content in lung tissue increased significantly on the 14th day after inhalation challenge of OVA compared to control. The ratio of CTGF mRNA /GAPDH mRNA in lung tissue in mice exposed to OVA increased 10-fold compared to those exposed to saline. Immunohistochemistry revealed that the number of CTGF-positive cells increased in bronchial submucosa after inhalation challenge of OVA. Conclusions: Our results suggested that CTGF might be one of the potential molecules involved in subepithelial fibrosis in murine airways with allergic inflammation.

Keywords

• asthma
• collagen
• remodeling
• subepithelial fibrosis
• TGF-β