PURPOSE: Emerging evidence supports a major role for a thrombospondin-1 (TSP-1) and transforming growth factor-β (TGF-β) axis in fibrotic disease. TSP-1 can activate latent TGF-β, an important profibrotic cytokine involved in various fibrotic diseases. The aim of this study is to evaluate a role of TSP-1 in pulmonary fibrosis.
METHODS: Serum and bronchoalveolar lavage fluid levels of TSP-1 were measured by a competitive enzyme immunoassay in patients with idiopathic interstitial pneumonias (IIPs). Expression and localization of TSP-1 in their lung specimens was analyzed by immunohistochemical staining. The inhibitory effect of suppression of TSP-1 was evaluated following the single intratracheal administration of TSP-1-siRNA in a mouse model of FITC-induced pulmonary fibrosis.
RESULTS: The serum TSP-1 levels were significantly higher in patients with IIPs than in those with the controls. These levels correlated inversely with the %VC. TSP-1 was overexpressed predominantly in the hyperplastic type 2 pneumocytes and alveolar macrophages in the lung. The administration of TSP-1-siRNA into FITC-injured mice limited the alveolitis and the accumulation of collagen in the lungs.
CONCLUSION: Our results suggest an association between the serum TSP-1 levels and the presence of interstitial fibrosis. The direct suppression of TSP-1 in the lung by the intratracheal administration of TSP-1-siRNA attenuated the development and progression of pulmonary fibrosis.
CLINICAL IMPLICATIONS: TSP-1 might have a potential as a molecular target for therapeutic intervention in the treatment of fibrotic lung diseases. Further studies are required.
DISCLOSURE: Hiroaki Oka, No Financial Disclosure Information; No Product/Research Disclosure Information